2. Academic Validation
  3. Tinagl1 Suppresses Triple-Negative Breast Cancer Progression and Metastasis by Simultaneously Inhibiting Integrin/FAK and EGFR Signaling

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

  • Cancer Cell. 2019 Jan 14;35(1):64-80.e7. doi: 10.1016/j.ccell.2018.11.016.
Minhong Shen 1,  Yi-Zhou Jiang 2,  Yong Wei 1,  Brian Ell 1,  Xinlei Sheng 1,  Mark Esposito 1,  Jooeun Kang 1,  Xiang Hang 1,  Hanqiu Zheng 1,  Michelle Rowicki 1,  Lanjing Zhang 3,  Weichung J Shih 4,  Toni Celià-Terrassa 1,  Yirong Liu 2,  IIeana Cristea 1,  Zhi-Ming Shao 2,  Yibin Kang 5
Affiliations

Affiliations

  • 1 Department of Molecular Biology, Princeton University, Washington Road, LTL 255, Princeton, NJ 08544, USA.
  • 2 Department of Breast Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China.
  • 3 Department of Pathology, University Medical Center of Princeton, Plainsboro, NJ, USA; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
  • 4 Department of Biostatistics, School of Public Health, Rutgers, The State University of New Jersey, 683 Hoes Lane West, Piscataway, NJ 08854, USA; Division of Biometrics, Rutgers Cancer Institute of New Jersey Rutgers, New Brunswick, NJ 08901, USA.
  • 5 Department of Molecular Biology, Princeton University, Washington Road, LTL 255, Princeton, NJ 08544, USA; Cancer Metabolism and Growth Program, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA. Electronic address: [email protected].
PMID: 30612941 DOI: 10.1016/j.ccell.2018.11.016
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.

Keywords

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

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-13535
    Integrin Antagonist