@article{db74cc53aaf947d79c2a95ed944960ee,
title = "Tinagl1 Suppresses Triple-Negative Breast Cancer Progression and Metastasis by Simultaneously Inhibiting Integrin/FAK and EGFR Signaling",
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",
author = "Minhong Shen and Jiang, {Yi Zhou} and Yong Wei and Brian Ell and Xinlei Sheng and Mark Esposito and Jooeun Kang and Xiang Hang and Hanqiu Zheng and Michelle Rowicki and Lanjing Zhang and Shih, {Weichung J.} and Toni Celi{\`a}-Terrassa and Yirong Liu and IIeana Cristea and Shao, {Zhi Ming} and Yibin Kang",
note = "Funding Information: We thank G. Ren, W. Li, L. Wan, H.A. Smith, Z. Li, W. Lu, and other lab members for technical support and helpful discussions, C. DeCoste and K. Rittenbach for assistance with flow cytometry, M. Alpern and V. Buynevich of the University Medical Center of Princeton at Plainsboro for assistance in blood sample analysis, and H. Matsumoto of Utsunomiya University for providing the Tinagl1 knockout mice. This research was supported by the Brewster Foundation , and grants from the US Department of Defense ( BC123187 ) (to Y.K.) and postdoctoral fellowships from Susan G. Komen (PDF17332118) and NJCCR (DFHS15PPCO21) (to M.S.). This research was also supported by the Pre-clinical Imaging and Flow Cytometry Shared Resources of the Rutgers Cancer Institute of New Jersey ( P30CA072720 ). Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2019",
month = jan,
day = "14",
doi = "10.1016/j.ccell.2018.11.016",
language = "English (US)",
volume = "35",
pages = "64--80.e7",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "1",
}