1. Academic Validation
  2. FAK-ERK activation in cell/matrix adhesion induced by the loss of apolipoprotein E stimulates the malignant progression of ovarian cancer

FAK-ERK activation in cell/matrix adhesion induced by the loss of apolipoprotein E stimulates the malignant progression of ovarian cancer

  • J Exp Clin Cancer Res. 2018 Feb 20;37(1):32. doi: 10.1186/s13046-018-0696-4.
Huiling Lai 1 Xuejiao Zhao 1 Yu Qin 1 Yi Ding 1 Ruqi Chen 1 Guannan Li 1 Marilyne Labrie 2 Zhiyong Ding 2 Jianfeng Zhou 1 Junbo Hu 1 Ding Ma 1 Yong Fang 3 Qinglei Gao 4
Affiliations

Affiliations

  • 1 Cancer Biology Research Center (Key laboratory of the ministry of education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jie Fang Avenue, Hankou, Wuhan, 430030, People's Republic of China.
  • 2 Department of Systems Biology, University of Texas MD Anderson Cancer Center, TX77030, Houston, USA.
  • 3 Cancer Biology Research Center (Key laboratory of the ministry of education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jie Fang Avenue, Hankou, Wuhan, 430030, People's Republic of China. yongfang@tjh.tjmu.edu.cn.
  • 4 Cancer Biology Research Center (Key laboratory of the ministry of education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jie Fang Avenue, Hankou, Wuhan, 430030, People's Republic of China. qlgao@tjh.tjmu.edu.cn.
Abstract

Background: Extracellular matrix (ECM) is a mediator of tumor progression. However, whether the alterations of the intraperitoneal ECM prior to tumor establishment affects the malignant progression of ovarian Cancer remains elusive.

Methods: Apolipoprotein (ApoE) knock-out mice was used to analyze the intraperitoneal ECM alterations by quantification of the major components of ECM. ID8 cells were implanted in vivo to generate allografts and human ovarian Cancer cell lines were characterized in vitro to assess the effects of ECM alterations on the malignant progression of ovarian Cancer. Adhesion assay, immunochemistry, cytokines profile, proliferation assay, transwell invasion assay and western blot were used to determine the malignant phenotype of ovarian Cancer cells.

Results: ApoE loss induced increased ECM deposition, which stimulated the adhesions of ovarian Cancer cells. The adhesion-mediated focal adhesion kinase (FAK) signaling enhanced the invasive behaviors of ovarian Cancer cells through activation of a ERK-MMP linkage. This ECM-induced signaling cascade was further confirmed in human ovarian Cancer cell lines in vitro. Furthermore, reversal of the ECM accumulation with BAPN or abrogation of adhesion-induced ERK activation in ovarian Cancer cells with MEK inhibitors (MEKi) was found to effectively delay ovarian Cancer progression.

Conclusions: These findings identify the FAK-ERK activation in cell/matrix adhesion in the malignant progression of ovarian Cancer and the efficiency of BAPN or MEKi for tumor suppression, providing an impetus for further studies to explore the possibility of new Anticancer therapeutic combinations.

Keywords

Adhesion; Apolipoprotein E; Extracellular matrix; Ovarian cancer; Tumor progression.

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