Integrin α5 down-regulation by miR-205 suppresses triple negative breast cancer stemness and metastasis by inhibiting the Src/Vav2/Rac1 pathway

Yajuan Xiao, Yunfei Li, Hua Tao, Brock Humphries, Aimin Li, Yiguo Jiang, Chengfeng Yang, Rongcheng Luo, Zhishan Wang

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

Triple negative breast cancer (TNBC) usually displays more aggressive metastasis, the underlying mechanism is unclear. Previous studies showed that microRNA-205 (miR-205) has controversial roles in cancer, however, its role in TNBC metastasis and the underlying mechanism have not been well-understood. In this study we found that miR-205 expression level is extremely low in basal mesenchymal-like highly migratory and invasive TNBC cells. Stably re-expressing miR-205 in TNBC cells significantly reduced their migration, invasion capability and cancer stem cell (CSC)-like property. Nude mouse orthotopic mammary xenograft tumor model study revealed that miR-205 re-expression greatly decreases TNBC tumor growth and abolishes spontaneous lung metastasis. Mechanistic studies demonstrated that miR-205 inhibits TNBC cell metastatic traits and tumor metastasis by down-regulating integrin α5 (ITGA5). Moreover, ITGA5 knockout using the CRISPR/Cas9 technique achieved the same strong inhibitory effect on TNBC cell CSC-like property and tumor metastasis as re-expressing miR-205 did. Further mechanistic studies indicated that ITGA5 down-regulation by miR-205 re-expression impairs TNBC cell metastatic traits by inhibiting the Src/Vav2/Rac1 pathway. Together, our findings suggest that miR-205 and ITGA5 may serve as potential targets for developing effective therapies for metastatic TNBC.

Original languageEnglish
Pages (from-to)199-209
Number of pages11
JournalCancer Letters
Volume433
DOIs
StatePublished - Oct 1 2018

Bibliographical note

Funding Information:
This study was supported in part by a Research Scholar Grant ( RGS-15-026-01-CSM ) from the American Cancer Society to C.Y. and a research grant from Elsa U. Pardee Foundation to Z.WPlease type the full funder name and country, plus grant IDs in the text, if available. Correctly acknowledging 'American Cancer Society to C.Y′ USA, 'Elsa U. Pardee Foundation' USA, Animal Imaging and Histology Resources of the University of Kentucky Markey Cancer Center USA. This research was also supported by the Shared Animal Imaging and Histology Resources of the University of Kentucky Markey Cancer Center ( P30CA177558 ).

Publisher Copyright:
© 2018 Elsevier B.V.

Keywords

  • Cancer stem cell (CSC)-Like property
  • Integrin α5 (ITGA5)
  • Metastatic triple negative breast cancer (TNBC)
  • Rho GTPase Rac1
  • microRNA-205 (miR-205)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Integrin α5 down-regulation by miR-205 suppresses triple negative breast cancer stemness and metastasis by inhibiting the Src/Vav2/Rac1 pathway'. Together they form a unique fingerprint.

Cite this