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Published on: October 27, 2014
Sur8 mediates tumorigenesis and metastasis in colorectal cancer
Young-Mi Lee1,2, Saluja Kaduwal1,2, Kug Hwa Lee1,2
1Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
Abstract:
Sur8, a scaffold protein of the Ras pathway, interacts with Ras and Raf and modulates the Ras-extracellular signal-regulated kinase (ERK) pathway. Here we show that Sur8 is overexpressed in established human colorectal cancer (CRC) cell lines and CRC patient tissues. Moreover, Sur8 expression is increased during liver metastasis in CRC patients. Sur8 knockdown decreases ERK and Akt activities in CRC cell lines, regardless of their K-Ras, B-Raf or PI3K mutation status. Overexpression or knockdown of Sur8 increases or decreases, respectively, the proliferation or transformation of CRC cell lines. Sur8 knockdown attenuates the migration and invasion of HCT116 CRC cells. Subcutaneous or orthotopic injection of HCT116 cells harboring a doxycycline (Dox)-mediated Sur8 knockdown system in nude mice resulted in decreased tumorigenic potential and inhibited the liver metastatic potential of HCT116 cells. Taken together, our data support the role of Sur8 as a promoter of tumorigenesis and liver metastasis in CRC through its modulation of the Ras-ERK and PI3K-Akt signaling pathways.
Insights
Sur8 protein promotes colorectal cancer (CRC) growth and liver metastasis by activating Ras-ERK and PI3K-Akt pathways. Reducing Sur8 levels inhibits CRC cell proliferation, migration, and tumor formation in mice.
Area of Science:
- Molecular Biology
- Oncology
- Cancer Research
Background:
- Sur8 is a scaffold protein involved in the Ras-extracellular signal-regulated kinase (ERK) pathway.
- The Ras-ERK pathway is frequently dysregulated in various cancers, including colorectal cancer (CRC).
Purpose of the Study:
- To investigate the role of Sur8 in colorectal cancer (CRC) tumorigenesis and metastasis.
- To elucidate the molecular mechanisms by which Sur8 influences CRC progression.
Main Methods:
- Analysis of Sur8 expression in human CRC cell lines and patient tissues.
- Sur8 knockdown experiments in CRC cell lines and in vivo mouse models.
- Assessment of cell proliferation, transformation, migration, invasion, and signaling pathway activities (ERK, Akt).
Main Results:
- Sur8 is overexpressed in CRC cell lines and patient tissues, with increased expression during liver metastasis.
- Sur8 knockdown reduces ERK and Akt activities, proliferation, migration, and invasion in CRC cells.
- In vivo studies demonstrated that Sur8 knockdown inhibits tumor growth and liver metastasis in mice.
Conclusions:
- Sur8 acts as a promoter of tumorigenesis and liver metastasis in colorectal cancer (CRC).
- Sur8 modulates CRC progression by influencing the Ras-ERK and PI3K-Akt signaling pathways.
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