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

80 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

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

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