Oncotarget

Research Papers:

Sur8/Shoc2 promotes cell motility and metastasis through activation of Ras-PI3K signaling

Saluja Kaduwal, Woo-Jeong Jeong, Jong-Chan Park, Kug Hwa Lee, Young-Mi Lee, Soung Hoo Jeon, Yong-Beom Lim, Do Sik Min and Kang-Yell Choi _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2015; 6:33091-33105. https://doi.org/10.18632/oncotarget.5173

Metrics: PDF 1409 views  |   HTML 1699 views  |   ?  


Abstract

Saluja Kaduwal1,2, Woo-Jeong Jeong1,2, Jong-Chan Park1,2, Kug Hwa Lee1,2, Young-Mi Lee1,2,5, Soung-Hoo Jeon1,2,6, Yong-Beom Lim1,3, Do Sik Min1,4, Kang-Yell Choi1,2

1Translational Research Center for Protein Function Control, Yonsei University, Seoul, 120-749, Korea

2Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-749, Korea

3Department of Materials Science and Engineering, Yonsei University, Seoul, 120-749, Korea

4Department of Molecular Biology, College of Natural Science, Pusan National University, Pusan, 609-735, Korea

5Current address: Division of Pharmacology and Translational Research, Hanmi Research Center, Hwaseong-si Gyeonggi-do, 445-813, Korea

6Current address: Department of Microbiology and Immunology, Xenotransplantation Research Center, Medical Research Center, Institute of Endemic Disease, Seoul National University College of Medicine, Seoul, 110-799, Korea

Correspondence to:

Kang-Yell Choi, e-mail: kychoi@yonsei.ac.kr

Keywords: Sur8, Ras, PI3K, cell migration, metastasis

Received: June 02, 2015     Accepted: August 26, 2015     Published: September 05, 2015

ABSTRACT

Sur8 (also known as Shoc2) is a Ras-Raf scaffold protein that modulates signaling through extracellular signal-regulated kinase (ERK) pathway. Although Sur8 has been shown to be a scaffold protein of the Ras-ERK pathway, its interaction with other signaling pathways and its involvement in tumor malignancy has not been reported. We identified that Sur8 interacts with the p110α subunit of phosphatidylinositol 3-kinase (PI3K), as well as with Ras and Raf, and these interactions are increased in an epidermal growth factor (EGF)- and oncogenic Ras-dependent manner. Sur8 regulates cell migration and invasion via activation of Rac and matrix metalloproteinases (MMPs). Interestingly, using inhibitors of MEK and PI3K we found Sur8 mediates these cellular behaviors predominantly through PI3K pathway. We further found that human metastatic melanoma tissues had higher Sur8 content followed by activations of Akt, ERK, and Rac. Lentivirus-mediated Sur8-knockdown attenuated metastatic potential of highly invasive B16-F10 melanoma cells indicating the role of Sur8 in melanoma metastasis. This is the first report to identify the role of scaffold protein Sur8 in regulating cell motility, invasion, and metastasis through activation of both ERK and PI3K pathways.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 5173