Tinagl1 Suppresses Triple-Negative Breast Cancer Progression and Metastasis by Simultaneously Inhibiting Integrin/FAK and EGFR Signaling

Minhong Shen, Yi Zhou Jiang, Yong Wei, Brian Ell, Xinlei Sheng, Mark Esposito, Jooeun Kang, Xiang Hang, Hanqiu Zheng, Michelle Rowicki, Lanjing Zhang, Weichung J. Shih, Toni Celià-Terrassa, Yirong Liu, IIeana Cristea, Zhi Ming Shao, Yibin Kang

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Triple-negative breast cancer (TNBC) patients have the worst prognosis and distant metastasis-free survival among all major subtypes of breast cancer. The poor clinical outlook is further exacerbated by a lack of effective targeted therapies for TNBC. Here we show that ectopic expression and therapeutic delivery of the secreted protein Tubulointerstitial nephritis antigen-like 1 (Tinagl1) suppresses TNBC progression and metastasis through direct binding to integrin α5β1, αvβ1, and epidermal growth factor receptor (EGFR), and subsequent simultaneous inhibition of focal adhesion kinase (FAK) and EGFR signaling pathways. Moreover, Tinagl1 protein level is associated with good prognosis and reversely correlates with FAK and EGFR activation status in TNBC. Our results suggest Tinagl1 as a candidate therapeutic agent for TNBC by dual inhibition of integrin/FAK and EGFR signaling pathways.

Original languageEnglish (US)
Pages (from-to)64-80.e7
JournalCancer Cell
Volume35
Issue number1
DOIs
StatePublished - Jan 14 2019

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cell Biology
  • Cancer Research

Keywords

  • EGFR
  • FAK
  • Tinagl1
  • extracellular matrix
  • integrin
  • metastasis
  • triple-negative breast cancer
  • tumor-stromal interaction

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