Aberrant activation of Wnt/catenin signaling and overexpression of ABCG2 contributes to apoptosis down regulation and tumor progression of high grade ovarian cancer

Zhaohua  Gui; Hong Yan; Jinfeng Wu; Mingxun  Zhang; Airan  Wu; Jie He

doi:10.18388/abp.2020_5488

Zhaohua Gui 1Department of Pathology, The First Affiliated Hospital of USTC, Division of life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, China; 2Intelligent Pathology Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, China; 3Department of Pathology, The First Affiliated Hospital of USTC, Division of life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230031, China
Hong Yan 1Department of Pathology, The First Affiliated Hospital of USTC, Division of life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, China; 2Intelligent Pathology Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, China; 3Department of Pathology, The First Affiliated Hospital of USTC, Division of life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230031, China
Jinfeng Wu 1Department of Pathology, The First Affiliated Hospital of USTC, Division of life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, China; 2Intelligent Pathology Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, China; 3Department of Pathology, The First Affiliated Hospital of USTC, Division of life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230031, China
Mingxun Zhang 1Department of Pathology, The First Affiliated Hospital of USTC, Division of life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, China; 2Intelligent Pathology Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, China; 3Department of Pathology, The First Affiliated Hospital of USTC, Division of life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230031, China
Airan Wu 1Department of Pathology, The First Affiliated Hospital of USTC, Division of life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, China; 2Intelligent Pathology Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, China; 3Department of Pathology, The First Affiliated Hospital of USTC, Division of life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230031, China
Jie He 1Department of Pathology, The First Affiliated Hospital of USTC, Division of life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, China; 2Intelligent Pathology Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, China; 3Department of Pathology, The First Affiliated Hospital of USTC, Division of life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230031, China https://orcid.org/0000-0002-3857-6318

DOI: https://doi.org/10.18388/abp.2020_5488

Abstract

Side Population (SP) cells are the small pool of CSC like progenitor cells, which are drug resistant and recapitulate tumor generation. The occurrence of SP cells is the major inference for attaining a better treatment and improved patient survival. In this work, we have isolated 6% SP cells from a high grade ovarian carcinoma. Our functional characterization of SP cells revealed that elevated ABCG2 and anti-apoptotic factors contribute to chemoresistance and increased life span of SP cells. Further, the overexpression of surface antigens, such as CD133 and CD117 in SP cells, are the key driving forces for high clonogenic and invasion properties of SP cells. More importantly, we found by RT-PCR aberrant activation and upregulation of Wnt/ β-catenin and its downstream targeting genes, such as DKK1 and AXIN2 in SP cells. These findings suggest that development of new anticancer drugs which target Wnt/β-catenin signaling might effectively exterminate the SP cells and aid in disease free survival.