Research Paper Volume 12, Issue 6 pp 5336—5351

Overexpressed ITGA2 contributes to paclitaxel resistance by ovarian cancer cells through the activation of the AKT/FoxO1 pathway

Linlin Ma 1, *, , Yan Sun 2, 3, *, , Dan Li 5, , Hansong Li 1, , Xin Jin 3, 4, , Dianyun Ren 2, 3, ,

  • 1 Department of Obstetrics and Gynecology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, R.P. China
  • 2 Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
  • 3 Sino-German Laboratory of Personalized Medicine for Pancreatic Cancer, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
  • 4 Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
  • 5 Cardiovascular Medicine Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
* Equal contribution

received: December 3, 2019 ; accepted: March 9, 2020 ; published: March 22, 2020 ;

https://doi.org/10.18632/aging.102954
How to Cite

Copyright © 2020 Ma et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Ovarian cancer is one of the most malignant tumors of the female reproductive system, with high invasiveness. The disease is a severe threat to women's health. The ITGA2 gene, which codes for integrin subunit α2, is involved in the proliferation, invasion, and metastasis of cancer cells. Although previous studies have shown that ITGA2 increases in ovarian cancer, the specific molecular mechanism of how ITGA2 promotes ovarian cancer proliferation and metastasis is still unclear. In this study, we confirmed that ITGA2 was elevated in ovarian cancer, which led to poor prognosis and survival. Overexpressed ITGA2 promoted the proliferation of ovarian cancer cells. We also found that ITGA2 regulated the phosphorylation of forkhead box O1 (FoxO1) by mediating AKT phosphorylation, which provided a reasonable explanation for ITGA2’s role in ovarian cancer’s resistance to albumin paclitaxel. In summary, ITGA2 could be used as a new therapeutic target and prognostic indicator in ovarian cancer.

Abbreviations

ITGA2: Integrin alpha 2; FoxO1: forkhead box O1; HPA: The Human Protein Atlas web tool; IHC: immunohistochemistry; OS: overall survival; TMA: tissue microarray; PTX: paclitaxel.