Lee Young-Mi, Kaduwal Saluja, Lee Kug Hwa, Park Jong-Chan, Jeong Woo-Jeong, Choi Kang-Yell
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
Translational Research Center for Protein Function Control, Yonsei University, Seoul, Korea.
Exp Mol Med. 2016 Jul 29;48(7):e249. doi: 10.1038/emm.2016.58.
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.
Sur8是Ras信号通路的一种支架蛋白，它与Ras和Raf相互作用，并调节Ras-细胞外信号调节激酶（ERK）信号通路。在此我们表明，Sur8在已建立的人结肠直肠癌（CRC）细胞系和CRC患者组织中过表达。此外，在CRC患者发生肝转移期间，Sur8表达增加。无论CRC细胞系的K-Ras、B-Raf或PI3K突变状态如何，Sur8基因敲低都会降低其ERK和Akt活性。Sur8的过表达或基因敲低分别增加或降低CRC细胞系的增殖或转化。Sur8基因敲低减弱了HCT116 CRC细胞的迁移和侵袭能力。在裸鼠中皮下或原位注射携带强力霉素（Dox）介导的Sur8基因敲低系统的HCT116细胞，导致其致瘤潜力降低，并抑制了HCT116细胞的肝转移潜力。综上所述，我们的数据支持Sur8通过调节Ras-ERK和PI3K-Akt信号通路，在CRC的肿瘤发生和肝转移中发挥促进作用。
