OncoTargets and Therapy (Nov 2020)

Human Positive Coactivator 4 Affects the Progression and Prognosis of Pancreatic Ductal Adenocarcinoma via the mTOR/P70s6k Signaling Pathway

  • Su X,
  • Yang Y,
  • Ma L,
  • Luo P,
  • Shen K,
  • Dai H,
  • Jiang Y,
  • Shuai L,
  • Liu Z,
  • You J,
  • Min K,
  • Shi C,
  • Chen Z

Journal volume & issue
Vol. Volume 13
pp. 12213 – 12223

Abstract

Read online

Xingxing Su,1,* Yishi Yang,1,* Le Ma,2,* Peng Luo,2 Kaicheng Shen,1 Haisu Dai,1 Yan Jiang,1 Ling Shuai,1 Zhipeng Liu,1 Jinshan You,1 Ke Min,1 Chunmeng Shi,2 Zhiyu Chen1 1Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, People’s Republic of China; 2Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing 400038, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhiyu ChenDepartment of Hepatobiliary Surgery, Southwest Hospital, First Affiliated Hospital of the Army Medical University, Chongqing 400038, People’s Republic of ChinaTel +86-13983881219Email [email protected] ShiInstitute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing 400038, People’s Republic of ChinaTel +86-13708396812Email [email protected]: Pancreatic cancer is one of the deadliest cancers in the world, and pancreatic ductal adenocarcinoma (PDAC) accounts for 90% of all cases. Human positive coactivator 4 (PC4) is a transcriptional coactivator that has been associated with the development and progression of several tumors. However, no studies investigated the potential role of PC4 in PDAC.Methods: We investigated PC4 expression in 81 PDAC tissue samples using immunohistochemistry and studied the impact of PC4 expression and the molecular mechanisms of this altered expression on PDAC tumorigenesis and proliferation both in vitro and in vivo.Results: PC4 overexpression was correlated with a poor outcome in PDAC patients. The RNAi-mediated knockdown of PC4 expression in CFPAC-1 and AsPC-1 cell lines reduced cell proliferation and tumor growth. The loss of PC4 in PDAC inhibits cell growth by inducing cell cycle arrest at the G1/S transition and suppressing the mTOR/p70s6k pathway.Discussion/Conclusion: Our findings reveal for the first time that PC4 exerts oncogenic functions by activating mTOR/p70s6k signaling pathway-mediated cell proliferation, implying that PC4 is a promising therapeutic target for PDAC.Keywords: PC4, PDAC, proliferation, mTOR/p70s6k

Keywords