Related Experiment Video
Updated: Dec 2, 2025
Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells
Published on: April 7, 2017
cMET promotes metastasis and epithelial-mesenchymal transition in colorectal carcinoma by repressing RKIP
Siyun Wang1, Haiqing Ma2, Yan Yan3
1Department of PET Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
Abstract:
Increasing evidence indicates that c-mesenchymal-epithelial transition factor (cMET) plays an important role in the malignant progression of colorectal cancer (CRC). However, the underlying mechanism is not fully understood. As a metastasis suppressor, raf kinase inhibitory protein (RKIP) loss has been reported in many cancer types. In this study, the expression levels of cMET and RKIP in CRC tissues and cell lines were determined, and their crosstalk and potential biological effects were explored in vitro and in vivo. Our results showed that cMET was inversely correlated with RKIP. Both cMET upregulation and RKIP downregulation indicated poor clinical outcomes. Moreover, the MAPK/ERK signaling pathway was implicated in the regulation of cMET and RKIP. Overexpression of cMET promoted tumor cell epithelial-mesenchymal transition, invasion, migration, and chemoresistance, whereas the effects could be efficiently inhibited by increased RKIP. Notably, small hairpin RNA-mediated cMET knockdown dramatically suppressed cell proliferation, although no RKIP-induced influence on cell growth was observed in CRC. Altogether, cMET overexpression may contribute to tumor progression by inhibiting the antioncogene RKIP, providing preclinical justification for targeting RKIP to treat cMET-induced metastasis of CRC.
Insights
Colorectal cancer (CRC) progression is linked to increased c-mesenchymal-epithelial transition factor (cMET) and decreased raf kinase inhibitory protein (RKIP). Restoring RKIP may offer a strategy against cMET-driven CRC metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The c-mesenchymal-epithelial transition factor (cMET) is increasingly implicated in colorectal cancer (CRC) malignancy.
- Raf kinase inhibitory protein (RKIP), a known metastasis suppressor, is often downregulated in various cancers.
Purpose of the Study:
- To investigate the relationship between cMET and RKIP expression in CRC.
- To explore their crosstalk and biological functions in CRC progression.
- To elucidate the role of the MAPK/ERK pathway in regulating cMET and RKIP.
Main Methods:
- Quantitative analysis of cMET and RKIP expression in CRC tissues and cell lines.
- In vitro and in vivo experiments to assess biological effects.
- Manipulation of cMET and RKIP levels (overexpression, knockdown) and assessment of tumor cell behavior.
- Analysis of the MAPK/ERK signaling pathway.
Main Results:
- cMET expression was inversely correlated with RKIP expression in CRC.
- Both high cMET and low RKIP levels correlated with poor clinical outcomes.
- cMET overexpression promoted epithelial-mesenchymal transition, invasion, migration, and chemoresistance, effects reversed by RKIP.
- cMET knockdown suppressed CRC cell proliferation, while RKIP had no significant effect on proliferation.
Conclusions:
- cMET overexpression contributes to CRC progression by suppressing the antioncogene RKIP.
- Targeting RKIP presents a potential therapeutic strategy for cMET-induced CRC metastasis.
Related Concept Videos
02:30Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
02:38Mitogens and the Cell Cycle