Upregulation of S100A10 in Metastasized Breast Cancer Stem Cells

Overview

Journal Cancer Sci

Specialty Oncology

Date 2020 Sep 25

PMID 32976661

Citations 16

Authors

Hisano Yanagi

Takashi Watanabe

Tatsunori Nishimura

Takanori Hayashi

Seishi Kono

Hitomi Tsuchida

Munetsugu Hirata

Yuko Kijima

Shintaro Takao

Seiji Okada

Motoshi Suzuki

Kazuyoshi Imaizumi

Kenji Kawada

Hironobu Minami

Noriko Gotoh

Yohei Shimono

Affiliations

Soon will be listed here.

Abstract

Metastatic progression remains the major cause of death in human breast cancer. Cancer cells with cancer stem cell (CSC) properties drive initiation and growth of metastases at distant sites. We have previously established the breast cancer patient-derived tumor xenograft (PDX) mouse model in which CSC marker CD44 cancer cells formed spontaneous microscopic metastases in the liver. In this PDX mouse, the expression levels of S100A10 and its family proteins were much higher in the CD44 cancer cells metastasized to the liver than those at the primary site. Knockdown of S100A10 in breast cancer cells suppressed and overexpression of S100A10 in breast cancer PDX cells enhanced their invasion abilities and 3D organoid formation capacities in vitro. Mechanistically, S100A10 regulated the matrix metalloproteinase activity and the expression levels of stem cell-related genes. Finally, constitutive knockdown of S100A10 significantly reduced their metastatic ability to the liver in vivo. These findings suggest that S100A10 functions as a metastasis promoter of breast CSCs by conferring both invasion ability and CSC properties in breast cancers.

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