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Sciellin mediates mesenchymal-to-epithelial transition in colorectal cancer hepatic metastasis.


ABSTRACT: Hepatic metastasis is the major cause of mortality in colorectal cancer (CRC) patients. Using proteomic analysis, we found sciellin (SCEL) to be specifically expressed in hepatic metastatic CRC cell lines. SCEL knockdown increased CRC cell migration and invasion, while overexpression had the opposite effect. SCEL knockdown also caused cancer cells to form more invasive structures within 3D cultures, increased the mesenchymal marker vimentin, and attenuated the epithelial marker E-cadherin. SCEL increased WNT signaling by activating ?-catenin and its downstream target c-myc, and activated mesenchymal-to-epithelial transition (MET) through a SCEL-?-catenin-E-cadherin axis. SCEL showed higher expression in late stage primary CRC than in its hepatic metastatic counterpart. SCEL expression is dynamically modulated by TGF-?1 and hypoxia, revealing a plastic MET mechanism for tumor colonization. Intrahepatic injection in immunodeficient mice revealed that SCEL is necessary for metastatic CRC tumor growth in the liver. These results demonstrate that SCEL is a MET inducer dynamically regulated through the metastasis process. They suggest SCEL may be a useful therapeutic target for preventing or eliminating CRC hepatic metastasis.

SUBMITTER: Chou CK 

PROVIDER: S-EPMC5041940 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Sciellin mediates mesenchymal-to-epithelial transition in colorectal cancer hepatic metastasis.

Chou Chuan-Kai CK   Fan Chi-Chen CC   Lin Pei-Shan PS   Liao Pei-Yu PY   Tung Jia-Chen JC   Hsieh Chang-Hsun CH   Hung Mien-Chie MC   Chen Chung-Hsuan CH   Chang Wei-Chao WC  

Oncotarget 20160501 18


Hepatic metastasis is the major cause of mortality in colorectal cancer (CRC) patients. Using proteomic analysis, we found sciellin (SCEL) to be specifically expressed in hepatic metastatic CRC cell lines. SCEL knockdown increased CRC cell migration and invasion, while overexpression had the opposite effect. SCEL knockdown also caused cancer cells to form more invasive structures within 3D cultures, increased the mesenchymal marker vimentin, and attenuated the epithelial marker E-cadherin. SCEL  ...[more]

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