title: Sur8 mediates tumorigenesis and metastasis in colorectal cancer.
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.
authors.affiliation: Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.|Translational Research Center for Protein Function Control, Yonsei University, Seoul, Korea.
authors.forename: Young-Mi
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.|Translational Research Center for Protein Function Control, Yonsei University, Seoul, Korea.
authors.forename: Saluja
authors.initials: S
authors.lastname: Kaduwal
authors.affiliation: Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.|Translational Research Center for Protein Function Control, Yonsei University, Seoul, Korea.
authors.forename: Kug Hwa
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.|Translational Research Center for Protein Function Control, Yonsei University, Seoul, Korea.
authors.forename: Jong-Chan
authors.initials: JC
authors.lastname: Park
authors.affiliation: Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.|Translational Research Center for Protein Function Control, Yonsei University, Seoul, Korea.
authors.forename: Woo-Jeong
authors.initials: WJ
authors.lastname: Jeong
authors.affiliation: Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.|Translational Research Center for Protein Function Control, Yonsei University, Seoul, Korea.
authors.forename: Kang-Yell
authors.initials: KY
authors.lastname: Choi
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics* / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D012007:Rectum / Q000378:metabolism / Q000473:pathology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C112913:SHOC2 protein, human