1. Academic Validation
  2. STYK1 promotes cancer cell proliferation and malignant transformation by activating PI3K-AKT pathway in gallbladder carcinoma

STYK1 promotes cancer cell proliferation and malignant transformation by activating PI3K-AKT pathway in gallbladder carcinoma

  • Int J Biochem Cell Biol. 2018 Apr;97:16-27. doi: 10.1016/j.biocel.2018.01.016.
Yun-Ping Hu 1 Zeng-Bin Wu 2 Lin Jiang 3 Yun-Peng Jin 3 Huai-Feng Li 3 Yi-Jian Zhang 3 Qiang Ma 3 Yuan-Yuan Ye 3 Zheng Wang 3 Yong-Chen Liu 3 Hong-Zhuan Chen 4 Ying-Bin Liu 5
Affiliations

Affiliations

  • 1 Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China; Shanghai Key Laboratory of Biliary Tract Disease Research, 1665 Kongjiang Road, Shanghai, 200092, China; Shanghai Research Center of Biliary Tract Disease, 1665 Kongjiang Road, Shanghai, 200092, China; Department of Pharmacology and Chemobiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • 2 Emergency Department, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
  • 3 Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China; Shanghai Key Laboratory of Biliary Tract Disease Research, 1665 Kongjiang Road, Shanghai, 200092, China; Shanghai Research Center of Biliary Tract Disease, 1665 Kongjiang Road, Shanghai, 200092, China.
  • 4 Department of Pharmacology and Chemobiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: yaoli@shsmu.edu.cn.
  • 5 Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China; Shanghai Key Laboratory of Biliary Tract Disease Research, 1665 Kongjiang Road, Shanghai, 200092, China; Shanghai Research Center of Biliary Tract Disease, 1665 Kongjiang Road, Shanghai, 200092, China. Electronic address: liuyingbin@xinhuamed.com.cn.
Abstract

Gallbladder carcinoma (GBC) is the most common malignancy of the biliary tract with extremely poor prognosis. The malignant transformation of GBC is associated with cell proliferation, invasion, and epithelial-mesenchymal transition (EMT). However, the molecular mechanisms underlying GBC progression are poorly understood. We found that serine threonine tyrosine kinase 1 (STYK1) was elevated in GBC and was negatively correlated with clinical outcomes and prognosis. Overexpression of STYK1 in GBC cell lines gave rise to increased cell proliferation, colony formation, migration and invasion, thus committing cells to undergoing EMT. In contrast, silence of STYK1 led to opposite effects on cell transformation. Consistent with STYK1 gene knockdown, Akt specific inhibitor MK2206 abrogated tumor promoting action induced by STYK1, suggesting that PI3K/Akt pathway is essential for the oncogenic role of STYK1 in GBC. STYK1 shRNA in GBC cells inhibited development of xenografted tumors compared with control cells. Collectively, our findings suggest that STYK1 is a critical regulator of tumor growth and metastasis, and may serve as a potential target for GBC therapy.

Keywords

AKT; Gallbladder carcinoma; Metastasis; Proliferation; STYK1.

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