PIK3CB is involved in metastasis through the regulation of cell adhesion to collagen I in pancreatic cancer

Journal of Advanced Research

Zhong Liu¹  Biao Zheng²  Stephen Jun Fei Chong²  Kengo Shirahane³  Kenoki Ohuchida⁴  Xianbin Zhang⁵  Masafumi Nakamura⁶  Jianhua Qu⁶  Haimin Feng⁶  Peng Gong⁷  Kazuhiro Mizumoto⁸  Rui Liang⁸ 

[1] Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan;Carson International Cancer Research Center, Shenzhen University General Hospital and Shenzhen University Clinical Medical Academy, Shenzhen, Guangdong 518055, China;Corresponding authors at: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, Japan (K. Ohuchida). Department of General Surgery, Shenzhen University General Hospital/Shenzhen University Clinical Medical Academy, 1098 Xueyuan Road, Shenzhen, Guangdong 518055, China (P Gong). Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, Japan (M. Nakamura).;Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore 117593, Singapore;Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan;;Department of General Surgery &Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA;Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan;

关键词: PIK3CB;    Adhesion;    Collagen I;    Metastasis;    Pancreatic cancer;   

DOI  :  

来源: DOAJ

【 摘 要 】

Introduction: Pancreatic adenocarcinoma (PAAD) is an aggressive malignancy, with a major mortality resulting from the rapid progression of metastasis. Unfortunately, no effective treatment strategy has been developed for PAAD metastasis to date. Thus, unraveling the mechanisms involved in PAAD metastatic phenotype may facilitate the treatment for PAAD patients. Objectives: PIK3CB is an oncogene implicated in cancer development and progression but less is known about whether PIK3CB participates in PAAD metastasis. Therefore, the objective of this study is to explore the mechanism(s) of PIK3CB in PAAD metastasis. Methods: In our study, we examined the PIK3CB expression pattern using bioinformatic analysis and clinical material derived from patients with PAAD. Subsequently, a series of biochemical experiments were conducted to investigate the role of PIK3CB as potential mechanism(s) underlying PAAD metastasis in vivo using nude mice and in vitro using cell lines. Results: We observed that PIK3CB was involved in PAAD progression. Notably, we identified that PIK3CB was involved in PAAD metastasis. Downregulation of PIK3CB significantly reduced PAAD metastatic potential in vivo. Furthermore, a series of bioinformatic analyses showed that PIK3CB was involved in cell adhesion in PAAD. Notably, PIK3CB depletion inhibited invasion potential specifically via suppressing cell adhesion to collagen I in PAAD cells. Conclusion: Collectively, our findings indicate that PIK3CB is involved in PAAD metastasis through cell-matrix adhesion. We proposed that PIK3CB is a potential therapeutic target for PAAD therapy.

【 授权许可】

Unknown