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

doi:10.1016/j.ccell.2018.11.016

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 journal › Article › peer-review

126 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 language	English (US)
Pages (from-to)	64-80.e7
Journal	Cancer Cell
Volume	35
Issue number	1
DOIs	https://doi.org/10.1016/j.ccell.2018.11.016
State	Published - Jan 14 2019

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

Keywords

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

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10.1016/j.ccell.2018.11.016

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Shen, M., Jiang, Y. Z., Wei, Y., Ell, B., Sheng, X., Esposito, M., Kang, J., Hang, X., Zheng, H., Rowicki, M., Zhang, L., Shih, W. J., Celià-Terrassa, T., Liu, Y., Cristea, II., Shao, Z. M., & Kang, Y. (2019). Tinagl1 Suppresses Triple-Negative Breast Cancer Progression and Metastasis by Simultaneously Inhibiting Integrin/FAK and EGFR Signaling. Cancer Cell, 35(1), 64-80.e7. https://doi.org/10.1016/j.ccell.2018.11.016

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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",

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year = "2019",

month = jan,

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doi = "10.1016/j.ccell.2018.11.016",

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Shen, M, Jiang, YZ, 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, ZM & Kang, Y 2019, 'Tinagl1 Suppresses Triple-Negative Breast Cancer Progression and Metastasis by Simultaneously Inhibiting Integrin/FAK and EGFR Signaling', Cancer Cell, vol. 35, no. 1, pp. 64-80.e7. https://doi.org/10.1016/j.ccell.2018.11.016

TY - JOUR

T1 - Tinagl1 Suppresses Triple-Negative Breast Cancer Progression and Metastasis by Simultaneously Inhibiting Integrin/FAK and EGFR Signaling

AU - Shen, Minhong

AU - Jiang, Yi Zhou

AU - Wei, Yong

AU - Ell, Brian

AU - Sheng, Xinlei

AU - Esposito, Mark

AU - Kang, Jooeun

AU - Hang, Xiang

AU - Zheng, Hanqiu

AU - Rowicki, Michelle

AU - Zhang, Lanjing

AU - Shih, Weichung J.

AU - Celià-Terrassa, Toni

AU - Liu, Yirong

AU - Cristea, IIeana

AU - Shao, Zhi Ming

AU - Kang, Yibin

PY - 2019/1/14

Y1 - 2019/1/14

N2 - 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.

AB - 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.

KW - EGFR

KW - FAK

KW - Tinagl1

KW - extracellular matrix

KW - integrin

KW - metastasis

KW - triple-negative breast cancer

KW - tumor-stromal interaction

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SN - 1535-6108

VL - 35

SP - 64-80.e7

JO - Cancer Cell

JF - Cancer Cell

IS - 1

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

Keywords

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