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

TitleTinagl1 Suppresses Triple-Negative Breast Cancer Progression and Metastasis by Simultaneously Inhibiting Integrin/FAK and EGFR Signaling.
Publication TypeJournal Article
Year of Publication2019
AuthorsShen, M, Jiang, Y-Z, Wei, Y, Ell, B, Sheng, X, Esposito, M, Kang, J, Hang, X, Zheng, H, Rowicki, M, Zhang, L, Shih, WJ, Celià-Terrassa, T, Liu, Y, Cristea, II, Shao, Z-M, Kang, Y
JournalCancer Cell
Volume35
Issue1
Pagination64-80.e7
Date Published2019 01 14
ISSN1878-3686
KeywordsAnimals, Biomarkers, Tumor, Cell Line, Tumor, Cell Movement, Cell Proliferation, Disease Progression, ErbB Receptors, Extracellular Matrix Proteins, Female, Focal Adhesion Kinase 1, Gene Expression Regulation, Neoplastic, Humans, Integrin alpha5beta1, Lipocalins, Lung Neoplasms, Mice, Prognosis, Receptors, Vitronectin, Signal Transduction, Triple Negative Breast Neoplasms
Abstract

<p>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.</p>

DOI10.1016/j.ccell.2018.11.016
Alternate JournalCancer Cell
PubMed ID30612941
Grant ListP30 CA072720 / CA / NCI NIH HHS / United States