Relevance of Mortalin to Cancer Cell Stemness and Cancer Therapy

Overview

Journal Sci Rep

Specialty Science

Date 2017 Feb 7

PMID 28165047

Citations 42

Authors

Chae-Ok Yun

Priyanshu Bhargava

Youjin Na

Jung-Sun Lee

Jihoon Ryu

Sunil C Kaul

Renu Wadhwa

Affiliations

Soon will be listed here.

Abstract

Mortalin/mtHsp70 is a member of Hsp70 family of proteins. Enriched in a large variety of cancers, it has been shown to contribute to the process of carcinogenesis by multiple ways including inactivation of tumor suppressor p53 protein, deregulation of apoptosis and activation of EMT signaling. In this study, we report that upregulation of mortalin contributes to cancer cell stemness. Several cancer cell stemness markers, such as ABCG2, OCT-4, CD133, ALDH1, CD9, MRP1 and connexin were upregulated in mortalin-overexpressing cells that showed higher ability to form spheroids. These cells also showed higher migration, and were less responsive to a variety of cancer chemotherapeutic drugs. Of note, knockdown of mortalin by specific shRNA sensitized these cells to all the drugs used in this study. We report that low doses of anti-mortalin molecules, MKT-077 and CAPE, also caused similar sensitization of cancer cells to chemotherapeutic drugs and hence are potential candidates for effective cancer chemotherapy.

Citing Articles

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Targeting HSP90 in Gynecologic Cancer: Molecular Mechanisms and Therapeutic Approaches.

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Targeting GRP75 with a Chlorpromazine Derivative Inhibits Endometrial Cancer Progression Through GRP75-IP3R-Ca-AMPK Axis.

Wang Q, Li L, Gao X, Zhang C, Xu C, Song L Adv Sci (Weinh). 2024; 11(15):e2304203.

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Human HSP70-escort protein 1 (hHep1) interacts with negatively charged lipid bilayers and cell membranes.

Moritz M, Dores-Silva P, Coto A, Selistre-de-Araujo H, Leitao A, Cauvi D Cell Stress Chaperones. 2023; 28(6):1001-1012.

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Clinical Relevance of Mortalin in Ovarian Cancer Patients.

Rajtak A, Czerwonka A, Pitter M, Kotarski J, Okla K Cells. 2023; 12(5).

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