Roles of the NR2F Family in the Development, Disease, and Cancer of the Lung
Abstract
:1. Introduction
2. NR2F Family in Lung Development and Non-Cancerous Diseases
3. NR2F Family in Primary Lung Cancer
4. NR2F Family in Metastatic Lung Cancer
5. Other Members of the Nuclear Receptor Superfamily Associated with the NR2F Family and Lung Cancer
5.1. Estrogen Receptors (ERs)
5.2. Progesterone Receptor (PR)
5.3. Retinoic Acid Receptors (RARs)
5.4. Retinoic X Receptors (RXRs)
5.5. Peroxisome-Proliferator-Activated Receptors (PPARs)
5.6. Vitamin D Receptors (VDRs)
5.7. Thyroid Hormone Receptors (TRs)
6. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Sever, R.; Glass, C.K. Signaling by nuclear receptors. Cold Spring Harb. Perspect. Biol. 2013, 5, a016709. [Google Scholar] [CrossRef]
- Parris, T.Z. Pan-cancer analyses of human nuclear receptors reveal transcriptome diversity and prognostic value across cancer types. Sci. Rep. 2020, 10, 1873. [Google Scholar] [CrossRef]
- Guzman, A.; Hughes, C.H.K.; Murphy, B.D. Orphan nuclear receptors in angiogenesis and follicular development. Reproduction 2021, 162, R35–R54. [Google Scholar] [CrossRef] [PubMed]
- Wang, L.H.; Tsai, S.Y.; Sagami, I.; Tsai, M.J.; O’Malley, B.W. Purification and characterization of chicken ovalbumin upstream promoter transcription factor from HeLa cells. J. Biol. Chem. 1987, 262, 16080–16086. [Google Scholar] [CrossRef] [PubMed]
- Wang, L.H.; Ing, N.H.; Tsai, S.Y.; O’Malley, B.W.; Tsai, M.J. The COUP-TFs compose a family of functionally related transcription factors. Gene Expr. 1991, 1, 207–216. [Google Scholar]
- Barnhart, K.M.; Mellon, P.L. The sequence of a murine cDNA encoding Ear-2, a nuclear orphan receptor. Gene 1994, 142, 313–314. [Google Scholar] [CrossRef]
- Park, J.I.; Tsai, S.Y.; Tsai, M.J. Molecular mechanism of chicken ovalbumin upstream promoter-transcription factor (COUP-TF) actions. Keio J. Med. 2003, 52, 174–181. [Google Scholar] [CrossRef] [PubMed]
- Leng, X.; Cooney, A.J.; Tsai, S.Y.; Tsai, M.J. Molecular mechanisms of COUP-TF-mediated transcriptional repression: Evidence for transrepression and active repression. Mol. Cell Biol. 1996, 16, 2332–2340. [Google Scholar] [CrossRef]
- Tang, K.; Tsai, S.Y.; Tsai, M.J. COUP-TFs and eye development. Biochim. Biophys. Acta 2015, 1849, 201–209. [Google Scholar] [CrossRef]
- Cooney, A.J.; Tsai, S.Y.; O’Malley, B.W.; Tsai, M.J. Chicken ovalbumin upstream promoter transcription factor (COUP-TF) dimers bind to different GGTCA response elements, allowing COUP-TF to repress hormonal induction of the vitamin D3, thyroid hormone, and retinoic acid receptors. Mol. Cell Biol. 1992, 12, 4153–4163. [Google Scholar] [CrossRef]
- Kruse, S.W.; Suino-Powell, K.; Zhou, X.E.; Kretschman, J.E.; Reynolds, R.; Vonrhein, C.; Xu, Y.; Wang, L.; Tsai, S.Y.; Tsai, M.J.; et al. Identification of COUP-TFII orphan nuclear receptor as a retinoic acid-activated receptor. PLoS Biol. 2008, 6, e227. [Google Scholar] [CrossRef] [PubMed]
- Armentano, M.; Chou, S.J.; Tomassy, G.S.; Leingartner, A.; O’Leary, D.D.; Studer, M. COUP-TFI regulates the balance of cortical patterning between frontal/motor and sensory areas. Nat. Neurosci. 2007, 10, 1277–1286. [Google Scholar] [CrossRef] [PubMed]
- Lodato, S.; Tomassy, G.S.; De Leonibus, E.; Uzcategui, Y.G.; Andolfi, G.; Armentano, M.; Touzot, A.; Gaztelu, J.M.; Arlotta, P.; Menendez de la Prida, L.; et al. Loss of COUP-TFI alters the balance between caudal ganglionic eminence- and medial ganglionic eminence-derived cortical interneurons and results in resistance to epilepsy. J. Neurosci. 2011, 31, 4650–4662. [Google Scholar] [CrossRef]
- Alzu’bi, A.; Lindsay, S.J.; Harkin, L.F.; McIntyre, J.; Lisgo, S.N.; Clowry, G.J. The Transcription Factors COUP-TFI and COUP-TFII have Distinct Roles in Arealisation and GABAergic Interneuron Specification in the Early Human Fetal Telencephalon. Cereb. Cortex 2017, 27, 4971–4987. [Google Scholar] [CrossRef] [PubMed]
- Yang, X.; Wan, R.; Liu, Z.; Feng, S.; Yang, J.; Jing, N.; Tang, K. The differentiation and integration of the hippocampal dorsoventral axis are controlled by two nuclear receptor genes. eLife 2023, 12, RP86940. [Google Scholar] [CrossRef]
- Bosch, D.G.; Boonstra, F.N.; Gonzaga-Jauregui, C.; Xu, M.; de Ligt, J.; Jhangiani, S.; Wiszniewski, W.; Muzny, D.M.; Yntema, H.G.; Pfundt, R.; et al. NR2F1 mutations cause optic atrophy with intellectual disability. Am. J. Hum. Genet. 2014, 94, 303–309. [Google Scholar] [CrossRef]
- Yang, X.; Feng, S.; Tang, K. COUP-TF Genes, Human Diseases, and the Development of the Central Nervous System in Murine Models. Curr. Top. Dev. Biol. 2017, 125, 275–301. [Google Scholar] [CrossRef]
- Zhang, K.; Yu, F.; Zhu, J.; Han, S.; Chen, J.; Wu, X.; Chen, Y.; Shen, T.; Liao, J.; Guo, W.; et al. Imbalance of Excitatory/Inhibitory Neuron Differentiation in Neurodevelopmental Disorders with an NR2F1 Point Mutation. Cell Rep. 2020, 31, 107521. [Google Scholar] [CrossRef]
- Yu, C.T.; Tang, K.; Suh, J.M.; Jiang, R.; Tsai, S.Y.; Tsai, M.J. COUP-TFII is essential for metanephric mesenchyme formation and kidney precursor cell survival. Development 2012, 139, 2330–2339. [Google Scholar] [CrossRef]
- Takamoto, N.; You, L.R.; Moses, K.; Chiang, C.; Zimmer, W.E.; Schwartz, R.J.; DeMayo, F.J.; Tsai, M.J.; Tsai, S.Y. COUP-TFII is essential for radial and anteroposterior patterning of the stomach. Development 2005, 132, 2179–2189. [Google Scholar] [CrossRef]
- You, L.R.; Takamoto, N.; Yu, C.T.; Tanaka, T.; Kodama, T.; Demayo, F.J.; Tsai, S.Y.; Tsai, M.J. Mouse lacking COUP-TFII as an animal model of Bochdalek-type congenital diaphragmatic hernia. Proc. Natl. Acad. Sci. USA 2005, 102, 16351–16356. [Google Scholar] [CrossRef]
- Pelaez-Garcia, A.; Barderas, R.; Batlle, R.; Vinas-Castells, R.; Bartolome, R.A.; Torres, S.; Mendes, M.; Lopez-Lucendo, M.; Mazzolini, R.; Bonilla, F.; et al. A proteomic analysis reveals that Snail regulates the expression of the nuclear orphan receptor Nuclear Receptor Subfamily 2 Group F Member 6 (Nr2f6) and interleukin 17 (IL-17) to inhibit adipocyte differentiation. Mol. Cell Proteom. 2015, 14, 303–315. [Google Scholar] [CrossRef] [PubMed]
- Klepsch, V.; Hermann-Kleiter, N.; Do-Dinh, P.; Jakic, B.; Offermann, A.; Efremova, M.; Sopper, S.; Rieder, D.; Krogsdam, A.; Gamerith, G.; et al. Nuclear receptor NR2F6 inhibition potentiates responses to PD-L1/PD-1 cancer immune checkpoint blockade. Nat. Commun. 2018, 9, 1538. [Google Scholar] [CrossRef]
- Qin, J.; Chen, X.; Xie, X.; Tsai, M.J.; Tsai, S.Y. COUP-TFII regulates tumor growth and metastasis by modulating tumor angiogenesis. Proc. Natl. Acad. Sci. USA 2010, 107, 3687–3692. [Google Scholar] [CrossRef]
- Qin, J.; Wu, S.P.; Creighton, C.J.; Dai, F.; Xie, X.; Cheng, C.M.; Frolov, A.; Ayala, G.; Lin, X.; Feng, X.H.; et al. COUP-TFII inhibits TGF-beta-induced growth barrier to promote prostate tumorigenesis. Nature 2013, 493, 236–240. [Google Scholar] [CrossRef] [PubMed]
- Wang, L.; Long, H.; Zheng, Q.; Bo, X.; Xiao, X.; Li, B. Circular RNA circRHOT1 promotes hepatocellular carcinoma progression by initiation of NR2F6 expression. Mol. Cancer 2019, 18, 119. [Google Scholar] [CrossRef]
- Xu, M.; Qin, J.; Tsai, S.Y.; Tsai, M.J. The role of the orphan nuclear receptor COUP-TFII in tumorigenesis. Acta Pharmacol. Sin. 2015, 36, 32–36. [Google Scholar] [CrossRef]
- Sajinovic, T.; Baier, G. New Insights into the Diverse Functions of the NR2F Nuclear Orphan Receptor Family. Front. Biosci. 2023, 28, 13. [Google Scholar] [CrossRef]
- Zhang, Y.; Zheng, A.; Xu, R.; Zhou, F.; Hao, A.; Yang, H.; Yang, P. NR2F1-induced NR2F1-AS1 promotes esophageal squamous cell carcinoma progression via activating Hedgehog signaling pathway. Biochem. Biophys. Res. Commun. 2019, 519, 497–504. [Google Scholar] [CrossRef]
- Bertacchi, M.; Parisot, J.; Studer, M. The pleiotropic transcriptional regulator COUP-TFI plays multiple roles in neural development and disease. Brain Res. 2019, 1705, 75–94. [Google Scholar] [CrossRef]
- Herriges, M.; Morrisey, E.E. Lung development: Orchestrating the generation and regeneration of a complex organ. Development 2014, 141, 502–513. [Google Scholar] [CrossRef]
- Bellusci, S.; Grindley, J.; Emoto, H.; Itoh, N.; Hogan, B.L. Fibroblast growth factor 10 (FGF10) and branching morphogenesis in the embryonic mouse lung. Development 1997, 124, 4867–4878. [Google Scholar] [CrossRef] [PubMed]
- Park, W.Y.; Miranda, B.; Lebeche, D.; Hashimoto, G.; Cardoso, W.V. FGF-10 is a chemotactic factor for distal epithelial buds during lung development. Dev. Biol. 1998, 201, 125–134. [Google Scholar] [CrossRef]
- Weaver, M.; Dunn, N.R.; Hogan, B.L. Bmp4 and Fgf10 play opposing roles during lung bud morphogenesis. Development 2000, 127, 2695–2704. [Google Scholar] [CrossRef]
- Que, J.; Luo, X.; Schwartz, R.J.; Hogan, B.L. Multiple roles for Sox2 in the developing and adult mouse trachea. Development 2009, 136, 1899–1907. [Google Scholar] [CrossRef]
- Tompkins, D.H.; Besnard, V.; Lange, A.W.; Keiser, A.R.; Wert, S.E.; Bruno, M.D.; Whitsett, J.A. Sox2 activates cell proliferation and differentiation in the respiratory epithelium. Am. J. Respir. Cell Mol. Biol. 2011, 45, 101–110. [Google Scholar] [CrossRef]
- Schittny, J.C. Development of the lung. Cell Tissue Res. 2017, 367, 427–444. [Google Scholar] [CrossRef]
- Kimura, Y.; Suzuki, T.; Kaneko, C.; Darnel, A.D.; Moriya, T.; Suzuki, S.; Handa, M.; Ebina, M.; Nukiwa, T.; Sasano, H. Retinoid receptors in the developing human lung. Clin. Sci. 2002, 103, 613–621. [Google Scholar] [CrossRef] [PubMed]
- Miao, Y.; Tan, C.; Pek, N.M.; Yu, Z.; Iwasawa, K.; Kechele, D.O.; Sundaram, N.; Pastrana-Gomez, V.; Kishimoto, K.; Yang, M.C.; et al. Deciphering Endothelial and Mesenchymal Organ Specification in Vascularized Lung and Intestinal Organoids. bioRxiv 2024. [Google Scholar] [CrossRef]
- Schupp, J.C.; Adams, T.S.; Cosme, C., Jr.; Raredon, M.S.B.; Yuan, Y.; Omote, N.; Poli, S.; Chioccioli, M.; Rose, K.A.; Manning, E.P.; et al. Integrated Single-Cell Atlas of Endothelial Cells of the Human Lung. Circulation 2021, 144, 286–302. [Google Scholar] [CrossRef]
- Shimamura, Y.; Tanaka, J.; Kakiuchi, M.; Sarmah, H.; Miura, A.; Hwang, Y.; Sawada, A.; Ninish, Z.; Yamada, K.; Mori, M.; et al. A developmental program that regulates mammalian organ size offsets evolutionary distance. bioRxiv 2022. [Google Scholar] [CrossRef]
- Tran, T.T.T.; Hung, J.J. PTEN decreases NR2F1 expression to inhibit ciliogenesis during EGFR(L858R)-induced lung cancer progression. Cell Death Dis. 2024, 15, 225. [Google Scholar] [CrossRef]
- Klaassens, M.; van Dooren, M.; Eussen, H.J.; Douben, H.; den Dekker, A.T.; Lee, C.; Donahoe, P.K.; Galjaard, R.J.; Goemaere, N.; de Krijger, R.R.; et al. Congenital diaphragmatic hernia and chromosome 15q26: Determination of a candidate region by use of fluorescent in situ hybridization and array-based comparative genomic hybridization. Am. J. Hum. Genet. 2005, 76, 877–882. [Google Scholar] [CrossRef]
- Wang, L.; Li, Z.; Wan, R.; Pan, X.; Li, B.; Zhao, H.; Yang, J.; Zhao, W.; Wang, S.; Wang, Q.; et al. Single-Cell RNA Sequencing Provides New Insights into Therapeutic Roles of Thyroid Hormone in Idiopathic Pulmonary Fibrosis. Am. J. Respir. Cell Mol. Biol. 2023, 69, 456–469. [Google Scholar] [CrossRef]
- Li, L.; Galichon, P.; Xiao, X.; Figueroa-Ramirez, A.C.; Tamayo, D.; Lee, J.J.K.; Kalocsay, M.; Gonzalez-Sanchez, D.; Chancay, S.; Bonventre, J.V.; et al. Orphan nuclear receptor COUP-TFII drives the myofibroblast metabolic shift leading to fibrosis. bioRxiv 2020. [Google Scholar] [CrossRef]
- Kim, W.; Giannikou, K.; Dreier, J.R.; Lee, S.; Tyburczy, M.E.; Silverman, E.K.; Radzikowska, E.; Wu, S.; Wu, C.L.; Henske, E.P.; et al. A genome-wide association study implicates NR2F2 in lymphangioleiomyomatosis pathogenesis. Eur. Respir. J. 2019, 53, 1900329. [Google Scholar] [CrossRef] [PubMed]
- Relli, V.; Trerotola, M.; Guerra, E.; Alberti, S. Abandoning the Notion of Non-Small Cell Lung Cancer. Trends Mol. Med. 2019, 25, 585–594. [Google Scholar] [CrossRef] [PubMed]
- Alberti, S.; Nutini, M.; Herzenberg, L.A. DNA methylation prevents the amplification of TROP1, a tumor-associated cell surface antigen gene. Proc. Natl. Acad. Sci. USA 1994, 91, 5833–5837. [Google Scholar] [CrossRef]
- Nasr, A.F.; Nutini, M.; Palombo, B.; Guerra, E.; Alberti, S. Mutations of TP53 induce loss of DNA methylation and amplification of the TROP1 gene. Oncogene 2003, 22, 1668–1677. [Google Scholar] [CrossRef]
- Sanchez-Danes, A.; Blanpain, C. Deciphering the cells of origin of squamous cell carcinomas. Nat. Rev. Cancer 2018, 18, 549–561. [Google Scholar] [CrossRef]
- Kim, E.J.; Kim, J.S.; Lee, S.; Cheon, I.; Kim, S.R.; Ko, Y.H.; Kang, K.; Tan, X.; Kurie, J.M.; Ahn, Y.H. ZEB1-regulated lnc-Nr2f1 promotes the migration and invasion of lung adenocarcinoma cells. Cancer Lett. 2022, 533, 215601. [Google Scholar] [CrossRef]
- Navab, R.; Gonzalez-Santos, J.M.; Johnston, M.R.; Liu, J.; Brodt, P.; Tsao, M.S.; Hu, J. Expression of chicken ovalbumin upstream promoter-transcription factor II enhances invasiveness of human lung carcinoma cells. Cancer Res. 2004, 64, 5097–5105. [Google Scholar] [CrossRef]
- Liu, W.; Zhou, Y.; Duan, W.; Song, J.; Wei, S.; Xia, S.; Wang, Y.; Du, X.; Li, E.; Ren, C.; et al. Glutathione peroxidase 4-dependent glutathione high-consumption drives acquired platinum chemoresistance in lung cancer-derived brain metastasis. Clin. Transl. Med. 2021, 11, e517. [Google Scholar] [CrossRef]
- Jin, C.; Xiao, L.; Zhou, Z.; Zhu, Y.; Tian, G.; Ren, S. MiR-142-3p suppresses the proliferation, migration and invasion through inhibition of NR2F6 in lung adenocarcinoma. Hum. Cell 2019, 32, 437–446. [Google Scholar] [CrossRef] [PubMed]
- Yoo, S.S.; Hong, M.J.; Lee, J.H.; Choi, J.E.; Lee, S.Y.; Lee, J.; Cha, S.I.; Kim, C.H.; Seok, Y.; Lee, E.; et al. Association between polymorphisms in microRNA target sites and survival in early-stage non-small cell lung cancer. Thorac. Cancer 2017, 8, 682–686. [Google Scholar] [CrossRef]
- Klepsch, V.; Siegmund, K.; Baier, G. Emerging Next-Generation Target for Cancer Immunotherapy Research: The Orphan Nuclear Receptor NR2F6. Cancers 2021, 13, 2600. [Google Scholar] [CrossRef] [PubMed]
- Doi, T.; Sugimoto, K.; Puri, P. Prenatal retinoic acid up-regulates pulmonary gene expression of COUP-TFII, FOG2, and GATA4 in pulmonary hypoplasia. J. Pediatr. Surg. 2009, 44, 1933–1937. [Google Scholar] [CrossRef] [PubMed]
- Zhang, C.; Wu, S.; Song, R.; Liu, C. Long noncoding RNA NR2F1-AS1 promotes the malignancy of non-small cell lung cancer via sponging microRNA-493-5p and thereby increasing ITGB1 expression. Aging 2020, 13, 7660–7675. [Google Scholar] [CrossRef] [PubMed]
- Jin, L.; Chen, C.; Huang, L.; Sun, Q.; Bu, L. Long noncoding RNA NR2F1-AS1 stimulates the tumorigenic behavior of non-small cell lung cancer cells by sponging miR-363-3p to increase SOX4. Open Med. 2022, 17, 87–95. [Google Scholar] [CrossRef]
- Jassim, A.; Rahrmann, E.P.; Simons, B.D.; Gilbertson, R.J. Cancers make their own luck: Theories of cancer origins. Nat. Rev. Cancer 2023, 23, 710–724. [Google Scholar] [CrossRef]
- Fares, J.; Fares, M.Y.; Khachfe, H.H.; Salhab, H.A.; Fares, Y. Molecular principles of metastasis: A hallmark of cancer revisited. Signal Transduct. Target. Ther. 2020, 5, 28. [Google Scholar] [CrossRef] [PubMed]
- Chaffer, C.L.; Weinberg, R.A. A perspective on cancer cell metastasis. Science 2011, 331, 1559–1564. [Google Scholar] [CrossRef] [PubMed]
- Altorki, N.K.; Markowitz, G.J.; Gao, D.; Port, J.L.; Saxena, A.; Stiles, B.; McGraw, T.; Mittal, V. The lung microenvironment: An important regulator of tumour growth and metastasis. Nat. Rev. Cancer 2019, 19, 9–31. [Google Scholar] [CrossRef] [PubMed]
- Giancotti, F.G. Mechanisms governing metastatic dormancy and reactivation. Cell 2013, 155, 750–764. [Google Scholar] [CrossRef]
- Singh, D.K.; Carcamo, S.; Farias, E.F.; Hasson, D.; Zheng, W.; Sun, D.; Huang, X.; Cheung, J.; Nobre, A.R.; Kale, N.; et al. 5-Azacytidine- and retinoic-acid-induced reprogramming of DCCs into dormancy suppresses metastasis via restored TGF-beta-SMAD4 signaling. Cell Rep. 2023, 42, 112560. [Google Scholar] [CrossRef]
- Liu, Y.; Zhang, P.; Wu, Q.; Fang, H.; Wang, Y.; Xiao, Y.; Cong, M.; Wang, T.; He, Y.; Ma, C.; et al. Long non-coding RNA NR2F1-AS1 induces breast cancer lung metastatic dormancy by regulating NR2F1 and DeltaNp63. Nat. Commun. 2021, 12, 5232. [Google Scholar] [CrossRef] [PubMed]
- Gao, X.L.; Zheng, M.; Wang, H.F.; Dai, L.L.; Yu, X.H.; Yang, X.; Pang, X.; Li, L.; Zhang, M.; Wang, S.S.; et al. NR2F1 contributes to cancer cell dormancy, invasion and metastasis of salivary adenoid cystic carcinoma by activating CXCL12/CXCR4 pathway. BMC Cancer 2019, 19, 743. [Google Scholar] [CrossRef]
- Jiang, Y.; Liu, X.; Shen, R.; Gu, X.; Qian, W. Fbxo21 regulates the epithelial-to-mesenchymal transition through ubiquitination of Nr2f2 in gastric cancer. J. Cancer 2021, 12, 1421–1430. [Google Scholar] [CrossRef]
- Liu, Y.; Chen, S.; Cai, K.; Zheng, D.; Zhu, C.; Li, L.; Wang, F.; He, Z.; Yu, C.; Sun, C. Hypoxia-induced long noncoding RNA NR2F1-AS1 maintains pancreatic cancer proliferation, migration, and invasion by activating the NR2F1/AKT/mTOR axis. Cell Death Dis. 2022, 13, 232. [Google Scholar] [CrossRef]
- Weikum, E.R.; Liu, X.; Ortlund, E.A. The nuclear receptor superfamily: A structural perspective. Protein Sci. 2018, 27, 1876–1892. [Google Scholar] [CrossRef]
- Gangwar, S.K.; Kumar, A.; Yap, K.C.; Jose, S.; Parama, D.; Sethi, G.; Kumar, A.P.; Kunnumakkara, A.B. Targeting Nuclear Receptors in Lung Cancer-Novel Therapeutic Prospects. Pharmaceuticals 2022, 15, 624. [Google Scholar] [CrossRef]
- Jeong, Y.; Xie, Y.; Xiao, G.; Behrens, C.; Girard, L.; Wistuba, I.I.; Minna, J.D.; Mangelsdorf, D.J. Nuclear receptor expression defines a set of prognostic biomarkers for lung cancer. PLoS Med. 2010, 7, e1000378. [Google Scholar] [CrossRef] [PubMed]
- More, E.; Fellner, T.; Doppelmayr, H.; Hauser-Kronberger, C.; Dandachi, N.; Obrist, P.; Sandhofer, F.; Paulweber, B. Activation of the MAP kinase pathway induces chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) expression in human breast cancer cell lines. J. Endocrinol. 2003, 176, 83–94. [Google Scholar] [CrossRef]
- Metivier, R.; Gay, F.A.; Hubner, M.R.; Flouriot, G.; Salbert, G.; Gannon, F.; Kah, O.; Pakdel, F. Formation of an hER alpha-COUP-TFI complex enhances hER alpha AF-1 through Ser118 phosphorylation by MAPK. EMBO J. 2002, 21, 3443–3453. [Google Scholar] [CrossRef]
- Kaiser, U.; Hofmann, J.; Schilli, M.; Wegmann, B.; Klotz, U.; Wedel, S.; Virmani, A.K.; Wollmer, E.; Branscheid, D.; Gazdar, A.F.; et al. Steroid-hormone receptors in cell lines and tumor biopsies of human lung cancer. Int. J. Cancer 1996, 67, 357–364. [Google Scholar] [CrossRef]
- Canver, C.C.; Memoli, V.A.; Vanderveer, P.L.; Dingivan, C.A.; Mentzer, R.M., Jr. Sex hormone receptors in non-small-cell lung cancer in human beings. J. Thorac. Cardiovasc. Surg. 1994, 108, 153–157. [Google Scholar] [CrossRef] [PubMed]
- Yang, M.H. Estrogen receptor in female lung carcinoma. Zhonghua Jie He He Hu Xi Za Zhi 1992, 15, 138–140+189. [Google Scholar]
- Chen, X.Q.; Zheng, L.X.; Li, Z.Y.; Lin, T.Y. Clinicopathological significance of oestrogen receptor expression in non-small cell lung cancer. J. Int. Med. Res. 2017, 45, 51–58. [Google Scholar] [CrossRef]
- Huang, Q.; Zhang, Z.; Liao, Y.; Liu, C.; Fan, S.; Wei, X.; Ai, B.; Xiong, J. 17beta-estradiol upregulates IL6 expression through the ERbeta pathway to promote lung adenocarcinoma progression. J. Exp. Clin. Cancer Res. 2018, 37, 133. [Google Scholar] [CrossRef] [PubMed]
- Tsai, S.Y.; Carlstedt-Duke, J.; Weigel, N.L.; Dahlman, K.; Gustafsson, J.A.; Tsai, M.J.; O’Malley, B.W. Molecular interactions of steroid hormone receptor with its enhancer element: Evidence for receptor dimer formation. Cell 1988, 55, 361–369. [Google Scholar] [CrossRef]
- Sanchez Calle, A.; Yamamoto, T.; Kawamura, Y.; Hironaka-Mitsuhashi, A.; Ono, M.; Tsuda, H.; Shimomura, A.; Tamura, K.; Takeshita, F.; Ochiya, T.; et al. Long non-coding NR2F1-AS1 is associated with tumor recurrence in estrogen receptor-positive breast cancers. Mol. Oncol. 2020, 14, 2271–2287. [Google Scholar] [CrossRef] [PubMed]
- Wetendorf, M.; DeMayo, F.J. Progesterone receptor signaling in the initiation of pregnancy and preservation of a healthy uterus. Int. J. Dev. Biol. 2014, 58, 95–106. [Google Scholar] [CrossRef] [PubMed]
- Stabile, L.P.; Dacic, S.; Land, S.R.; Lenzner, D.E.; Dhir, R.; Acquafondata, M.; Landreneau, R.J.; Grandis, J.R.; Siegfried, J.M. Combined analysis of estrogen receptor beta-1 and progesterone receptor expression identifies lung cancer patients with poor outcome. Clin. Cancer Res. 2011, 17, 154–164. [Google Scholar] [CrossRef]
- Mattern, J.; Klinga, K.; Runnebaum, B.; Volm, M. Influence of hormone therapy on human lung tumors transplanted into nude mice. Oncology 1985, 42, 388–390. [Google Scholar] [CrossRef]
- Laursen, K.B.; Mongan, N.P.; Zhuang, Y.; Ng, M.M.; Benoit, Y.D.; Gudas, L.J. Polycomb recruitment attenuates retinoic acid-induced transcription of the bivalent NR2F1 gene. Nucleic Acids Res. 2013, 41, 6430–6443. [Google Scholar] [CrossRef]
- Lin, B.; Chen, G.Q.; Xiao, D.; Kolluri, S.K.; Cao, X.; Su, H.; Zhang, X.K. Orphan receptor COUP-TF is required for induction of retinoic acid receptor beta, growth inhibition, and apoptosis by retinoic acid in cancer cells. Mol. Cell Biol. 2000, 20, 957–970. [Google Scholar] [CrossRef]
- Bushue, N.; Wan, Y.J. Retinoid pathway and cancer therapeutics. Adv. Drug Deliv. Rev. 2010, 62, 1285–1298. [Google Scholar] [CrossRef]
- Tang, X.H.; Gudas, L.J. Retinoids, retinoic acid receptors, and cancer. Annu. Rev. Pathol. 2011, 6, 345–364. [Google Scholar] [CrossRef]
- Gebert, J.F.; Moghal, N.; Frangioni, J.V.; Sugarbaker, D.J.; Neel, B.G. High frequency of retinoic acid receptor beta abnormalities in human lung cancer. Oncogene 1991, 6, 1859–1868. [Google Scholar]
- Houle, B.; Rochette-Egly, C.; Bradley, W.E. Tumor-suppressive effect of the retinoic acid receptor beta in human epidermoid lung cancer cells. Proc. Natl. Acad. Sci. USA 1993, 90, 985–989. [Google Scholar] [CrossRef] [PubMed]
- Xu, X.C.; Sozzi, G.; Lee, J.S.; Lee, J.J.; Pastorino, U.; Pilotti, S.; Kurie, J.M.; Hong, W.K.; Lotan, R. Suppression of retinoic acid receptor beta in non-small-cell lung cancer in vivo: Implications for lung cancer development. J. Natl. Cancer Inst. 1997, 89, 624–629. [Google Scholar] [CrossRef] [PubMed]
- Chang, Y.S.; Chung, J.H.; Shin, D.H.; Chung, K.Y.; Kim, Y.S.; Chang, J.; Kim, S.K.; Kim, S.K. Retinoic acid receptor-beta expression in stage I non-small cell lung cancer and adjacent normal appearing bronchial epithelium. Yonsei Med. J. 2004, 45, 435–442. [Google Scholar] [CrossRef]
- Germain, P.; Chambon, P.; Eichele, G.; Evans, R.M.; Lazar, M.A.; Leid, M.; De Lera, A.R.; Lotan, R.; Mangelsdorf, D.J.; Gronemeyer, H. International Union of Pharmacology. LXIII. Retinoid X receptors. Pharmacol. Rev. 2006, 58, 760–772. [Google Scholar] [CrossRef]
- Mangelsdorf, D.J.; Evans, R.M. The RXR heterodimers and orphan receptors. Cell 1995, 83, 841–850. [Google Scholar] [CrossRef]
- Kuznetsova, E.S.; Zinovieva, O.L.; Oparina, N.Y.; Prokofjeva, M.M.; Spirin, P.V.; Favorskaya, I.A.; Zborovskaya, I.B.; Lisitsyn, N.A.; Prassolov, V.S.; Mashkova, T.D. Abnormal expression of genes that regulate retinoid metabolism and signaling in non-small-cell lung cancer. Mol. Biol. 2016, 50, 255–265. [Google Scholar] [CrossRef]
- Ai, X.; Mao, F.; Shen, S.; Shentu, Y.; Wang, J.; Lu, S. Bexarotene inhibits the viability of non-small cell lung cancer cells via slc10a2/PPARgamma/PTEN/mTOR signaling pathway. BMC Cancer 2018, 18, 407. [Google Scholar] [CrossRef]
- Okamura, M.; Kudo, H.; Wakabayashi, K.; Tanaka, T.; Nonaka, A.; Uchida, A.; Tsutsumi, S.; Sakakibara, I.; Naito, M.; Osborne, T.F.; et al. COUP-TFII acts downstream of Wnt/beta-catenin signal to silence PPARgamma gene expression and repress adipogenesis. Proc. Natl. Acad. Sci. USA 2009, 106, 5819–5824. [Google Scholar] [CrossRef]
- Sasaki, H.; Tanahashi, M.; Yukiue, H.; Moiriyama, S.; Kobayashi, Y.; Nakashima, Y.; Kaji, M.; Kiriyama, M.; Fukai, I.; Yamakawa, Y.; et al. Decreased perioxisome proliferator-activated receptor gamma gene expression was correlated with poor prognosis in patients with lung cancer. Lung Cancer 2002, 36, 71–76. [Google Scholar] [CrossRef] [PubMed]
- Keshamouni, V.G.; Reddy, R.C.; Arenberg, D.A.; Joel, B.; Thannickal, V.J.; Kalemkerian, G.P.; Standiford, T.J. Peroxisome proliferator-activated receptor-gamma activation inhibits tumor progression in non-small-cell lung cancer. Oncogene 2004, 23, 100–108. [Google Scholar] [CrossRef]
- Sandgren, M.; Danforth, L.; Plasse, T.F.; DeLuca, H.F. 1,25-Dihydroxyvitamin D3 receptors in human carcinomas: A pilot study. Cancer Res. 1991, 51, 2021–2024. [Google Scholar]
- Srinivasan, M.; Parwani, A.V.; Hershberger, P.A.; Lenzner, D.E.; Weissfeld, J.L. Nuclear vitamin D receptor expression is associated with improved survival in non-small cell lung cancer. J. Steroid Biochem. Mol. Biol. 2011, 123, 30–36. [Google Scholar] [CrossRef] [PubMed]
- Mohamed, F.; Abdelaziz, A.O.; Kasem, A.H.; Ellethy, T.; Gayyed, M.F. Thyroid hormone receptor alpha1 acts as a new squamous cell lung cancer diagnostic marker and poor prognosis predictor. Sci. Rep. 2021, 11, 7944. [Google Scholar] [CrossRef] [PubMed]
- Iwasaki, Y.; Sunaga, N.; Tomizawa, Y.; Imai, H.; Iijima, H.; Yanagitani, N.; Horiguchi, K.; Yamada, M.; Mori, M. Epigenetic inactivation of the thyroid hormone receptor beta1 gene at 3p24.2 in lung cancer. Ann. Surg. Oncol. 2010, 17, 2222–2228. [Google Scholar] [CrossRef] [PubMed]
- Kwon, M.C.; Berns, A. Mouse models for lung cancer. Mol. Oncol. 2013, 7, 165–177. [Google Scholar] [CrossRef]
- Yang, Z.; Gimple, R.C.; Zhou, N.; Zhao, L.; Gustafsson, J.A.; Zhou, S. Targeting Nuclear Receptors for Cancer Therapy: Premises, Promises, and Challenges. Trends Cancer 2021, 7, 541–556. [Google Scholar] [CrossRef]
- Maniatis, S.; Petrescu, J.; Phatnani, H. Spatially resolved transcriptomics and its applications in cancer. Curr. Opin. Genet. Dev. 2021, 66, 70–77. [Google Scholar] [CrossRef]
- Zhang, Q.; Abdo, R.; Iosef, C.; Kaneko, T.; Cecchini, M.; Han, V.K.; Li, S.S. The spatial transcriptomic landscape of non-small cell lung cancer brain metastasis. Nat. Commun. 2022, 13, 5983. [Google Scholar] [CrossRef]
Disease Type | Genes | Functions | Models/Cell Lines/Tissues | Related Genes | Related Pathways | Reference | |
---|---|---|---|---|---|---|---|
Non-cancerous | CDH | Nr2f2↑ | May rescue lung hypoplasia and enhance lung growth | Nitrofen rat model of CDH | Fog2 and Gata4 | - | [57] |
Nr2f2↓ | Formation of CDH | Nkx3-2Cre/+; Nr2f2flox/flox mouse model | Fog2 | - | [21] | ||
NR2F2↓ | Formation of CDH | 15q deletion patients specimens | CHD2, RGMA and SIAT8B | - | [43] | ||
IPF | Nr2f2↑ | Decreases fibrosis | Bleomycin-treated mice model | Fn1 and Col1a1 | - | [44] | |
LAM | NR2F2↑ | Drives LAM pathogenesis | S-LAM patients specimens | MCTP2 and SPATA8 | - | [46] | |
Cancerous | NSCLC | NR2F1-AS1↓ | Decrease NSCLC cell proliferation, migration, and invasion and promoted tumor cell apoptosis | NSCLC patients specimens; BEAS-2B, H522, H460, H1299, A549 and SK-MES-1 cell lines; nude mice | - | NR2F1-AS1/miR-493-5p/ITGB1 pathway | [58] |
NSCLC | NR2F1-AS1↑ | Tumorigenic, promotes glycolysis and glutamine metabolism | NSCLC patients’ specimens; 16HBE, A549 and H522 cells | - | miR-363–3p/SOX4 axis | [59] | |
LUAD | NR2F6↑ | Promote proliferation, migration, invasion and enhances cell apoptosis | Lung adenocarcinoma patients specimens; A549, HCC827, HBE cells | miR-142-3p | - | [54] | |
Lung Carcinoma | NR2F2↑ | Promote cell invasion | A549, HeLa, NCI-H460, H661, H520, H441, MDAMB231 and H460SMcells | FAK(PTK2), MMP2, uPA and uPAR | - | [52] | |
LUAD | NR2F1↑ | Promote growth, migration, invasion, and tumorigenicity of lung adenocarcinoma cells | 393P, 344SQ, 412P, 307P, 344LN, 344P, 393LN, 531LN1, 531LN2, 531LN3, 531P1, 531P2, 713P, A549 and HCC827 cells | ZEB1 | ZEB1/NR2F1/NR2F1-AS1 axis | [51] | |
LUAD | NR2F2↑ | Induces platinum chemotherapeutic resistance in lung cancer brain metastasis | PC9, PC9-BrM1 and PC9-BrM3 cells; Nude mice | GSTM1 and GPX4 | Wnt signaling pathway | [53] |
Primary Cancer Types | Genes | Inhibition/Promotion Metastasis | Models/Cell Lines/Tissues | Related Genes | Related Pathways | Reference |
---|---|---|---|---|---|---|
Breast cancer | NR2F1-AS1↑ | Inhibition | BALB/c nude mice and NOD/SCID mice; CA1h-P1, CA1h-P2 and 4175-LM2 cells | PTBP and miR-205 | NR2F1/ΔNp63 axis | [66] |
Pancreatic cancer | NR2F1-AS1↑ | Promotion | PC and matched paracancerous tissue samples; BxPC-3, Capan-2, CFPAC-1, SW1990, MIA PaCa-2, PANC-1 and HPDE cells; nude mouse | NR2F1 | HIF pathway, AKT/mTOR pathway | [69] |
SACC | NR2F1↑ | Inhibition | SACC patients specimens; SACC-83 and SACC-LM cells; nude mice | - | CXCL12/ CXCR4 pathway | [67] |
HNSCC | NR2F1↑ | Inhibition | T-HEp3 cells and D-HEp3 cells; chicken chorioallantoic membrane (CAM) model; NU/J female mice model | - | TGF-β/SMAD4 signaling pathway | [65] |
Gastric cancer | Nr2f2↓ | Inhibition | Gastric cancer patients specimens; SGC-7901, BGC-823, MGC-803, MKN-45, MKN-28 and AGS cell lines; nude mice | Fbxo21 and Zeb1 | Nr2f2/Snail pathway | [68] |
Breast carcinoma | Nr2f2↓ | Inhibition | ROSA26CRE-ERT2/+; Nr2f2flox/floxmouse model and PyMT+/−/ROSA26CRE-ERT2/+; Nr2f2flox/flox mouse model; B16F10 and LLC cells | Ang-1 | VEGF signaling pathway | [24] |
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Yang, J.; Sun, W.; Cui, G. Roles of the NR2F Family in the Development, Disease, and Cancer of the Lung. J. Dev. Biol. 2024, 12, 24. https://doi.org/10.3390/jdb12030024
Yang J, Sun W, Cui G. Roles of the NR2F Family in the Development, Disease, and Cancer of the Lung. Journal of Developmental Biology. 2024; 12(3):24. https://doi.org/10.3390/jdb12030024
Chicago/Turabian StyleYang, Jiaxin, Wenjing Sun, and Guizhong Cui. 2024. "Roles of the NR2F Family in the Development, Disease, and Cancer of the Lung" Journal of Developmental Biology 12, no. 3: 24. https://doi.org/10.3390/jdb12030024