Cancer Stem Cell

Colorectal Cancer (CRC) is the second most common cancer in women and the third most common cancer in men. There is strong evidence for the role of Cancer Stem Cells (CSCs) in cancer progression. The identification and understanding CSCs genes such as LGR5 involved in the induction of cancer development is crucial in the prognosis of CRC. LGR5 is a membrane protein involved in several molecular signaling pathways, such as the Wnt signaling and NOTCH pathways. It has been shown that the LGR5 gene was overexpressed in CRC and is associated with the worst outcomes in patients with CRC, but molecular mechanisms of LGR5 in CRC development have been poorly identified. This review has summarized current studies about the role of stem cell marker of LGR5 in CRC progression. Future research in this area may improve the early detection of CRC, new therapies, and monitoring of CRC.

Metastatic colonization represents the final step of metastasis, and is the major cause of cancer mortality. Metastasis as an “inefficient” process requires the right population of tumor cells in a suitable microenvironment to form secondary tumors. Cancer stem cells are the only capable population of tumor cells to progress to overt metastasis. On the other hand, the occurrence of appropriate microenvironmental conditions within the target tissue would be critical for metastasis formation. Metastatic niche seems to be the specialized microenvironment to support tumor initiating cells at the distant organ. Master regulators not only determine cancer stem cell state, but also may have regulatory roles in metastatic niche elements. Meanwhile, both cancer stem cell and metastatic niche may function like two sides of the metastatic coin. Hypoxia inducible factors have multiple roles in regulation of both sides of this coin. TGF-β superfamily, also, have been considered as master regulators of epithelial to mesenchymal transition and metastasis and may play crucial roles in regulation of metastatic niche as well. In this regard, we hypothesize the presence of a possible emerging molecular pathway in the biological process of breast cancer metastasis. In this process, non-Smad TGF-β-induced metastasis connects cancer stem cell and metastatic niche formation through a central path, “Metastasis Pathway”.