An EGFR/Src-dependent β4 integrin/FAK complex contributes to malignancy of breast cancer

Tai, Yuling; Chu, Pei‐Yu; Lai, I-Rue; Wang, Mingyang; Tseng, Hui-Yuan; Guan, Jun‐Lin; Liou, Jun‐Yang; Shen, Tang‐Long

doi:10.1038/srep16408

Cited by 50 publications

(47 citation statements)

References 37 publications

(50 reference statements)

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“…In accordance with our previous study , we demonstrated that the activation of FAK arises via interaction with β4 integrin, resulting in FAK autophosphorylation at Tyr397 (Figs A and A,D). In this regard, a 25‐amino‐acid motif within the amino‐terminus of FAK was identified to be responsible for FAK interaction with β4 integrin (Fig.…”

Section: Discussionsupporting

confidence: 93%

“…S3B). Likewise, these results have been illustrated in human breast cancer recently . Together, our results demonstrated for the first time that β4 integrin interacts with FAK to form a complex in human colon cancer.…”

Section: Resultssupporting

confidence: 84%

“…Similar to our previous study [34], a triple mutation mutant, FAK E380A/K381A/Q382A , almost abolished FAK interaction with b4 integrin in HCT-116 cells, whereas b4 integrin binding remained intact with other FAK mutants of this 25-amino-acid motif such as FAK R385A/S386A (Fig. 2C).…”

Section: B4 Integrin Interacts With a 25-amino-acid Motif Within Thesupporting

confidence: 89%

“…In our previous study, we demonstrated a direct interaction between β4 integrin and FAK in human breast cancer . Therefore, we also examined whether β4 integrin interacts with FAK in human colon cancer.…”

Section: Resultsmentioning

confidence: 91%

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Activation of focal adhesion kinase through an interaction with β4 integrin contributes to tumorigenicity of colon cancer

et al. 2016

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Edited by Veli-Pekka LehtoHigh expression of either b4 integrin or focal adhesion kinase (FAK) has been reported in human colon cancer. However, it remains unclear how b4 integrin together with FAK contributes to the tumorigenicity of colon cancer. Here, we demonstrate that the co-overexpression of b4 integrin and FAK positively correlates with advanced stages of human colon cancer. Activated b4 integrin interacts with FAK and subsequently induces FAK phosphorylation at Tyr397. Furthermore, ablation of the b4 integrin/FAK complex and/or FAK activation impair colon cancer cell proliferation, anchorage-independent growth, and tumorigenicity. Our data indicate that the b4 integrin/FAK complex and subsequent FAK activation are essential regulators during the tumorigenicity of colon cancer, and we suggest an alternative strategy for colon cancer therapy.

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Section: Discussionsupporting

confidence: 93%

Section: Resultssupporting

confidence: 84%

Section: B4 Integrin Interacts With a 25-amino-acid Motif Within Thesupporting

confidence: 89%

Section: Resultsmentioning

confidence: 91%

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Activation of focal adhesion kinase through an interaction with β4 integrin contributes to tumorigenicity of colon cancer

et al. 2016

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“…p16 is a cyclin‐dependent kinase inhibitor that could cause pRb hypophosphorylation, which is crucial for long‐term maintenance of senescence . As mentioned above, ITGB4 is a complex structural adhesion molecule that could interact complexly with mitogen‐activated protein kinase, focal adhesion kinase, epidermal growth factor receptor and many other signaling molecules . In this paper, our study further showed that ITGB4 deficiency in airway epithelial cells could activate the p53 signaling pathway.…”

Section: Discussionsupporting

confidence: 60%

ITGB4 deficiency induces senescence of airway epithelial cells through p53 activation

Lin

Tang

et al. 2019

The FEBS Journal

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Aging is characterized by a progressive loss of physiological integrity, leading to impaired organ function and, ultimately, increased vulnerability to death. Many complex diseases are related to aging, including asthma. In the lung, the airway epithelium serves as the first barrier to prevent the access of inspired external stimuli and dictates the initial stress responses. Notably, in the airway mucosa of asthma patients, an increase in senescent airway epithelial cells has been detected. Although it has been speculated that the senescence of airway epithelial cells could increase asthma susceptibility and aggravate asthma severity, the role of cell senescence in the development of asthma remains unclear. Integrin β4 (ITGB4) is a structural adhesion molecule with complex physiological functions that is downregulated in airway epithelial cells of asthma patients. This study demonstrates that the expression of ITGB4 in airway epithelial cells is downregulated significantly under oxidative stress or upon inflammatory stimulation. Moreover, we show that ITGB4 deficiency induces the senescence of airway epithelial cells through the activation of the p53 pathway both in vitro and in vivo. Together, our results demonstrate that airway epithelial senescence induced by ITGB4 deficiency after oxidative stress or inflammatory stimulation may be involved in the pathogenesis of asthma. Understanding the contribution of ITGB4 deficiency to the senescence of airway epithelial cells in asthma patients may provide new therapeutic approaches for the treatment of asthma.

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Invasion and migration of MDA‐MB‐231 cells are inhibited by block of AhR and NFAT: role of AhR/NFAT1/β4 integrin signaling

Shadboorestan

Tarfiei

Montazeri

et al. 2018

J of Applied Toxicology

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Benzo[α]pyrene (BaP) can have significant role in the development of breast cancer via aryl hydrocarbon receptor (AhR) activation. AhR activation has been studied in several functions such as survival, migration and invasion of cancer cells. In cancer, integrins contribute to the migration/invasion process and are regulated by nuclear factor of activated T cells (NFAT) and transforming growth factor (TGF) beta pathways. The aim of the present study was to examine the effect of BaP, an activator of AhR and cyclosporine A (CsA), as inhibitor of NFAT on migration and invasion of MDA‐MB‐231 cells. Furthermore, the effects of BaP and CsA were evaluated regarding the crosstalk of AhR, NFAT1 and TGF‐β receptor 1 signaling. Treatment of MDA‐MB‐231 with BaP resulted in significantly more live cells in low doses; however, blocking NFAT with CsA decreased the viability of the cells. Activation of AhR by BaP induced invasion as well as migration in MDA‐MB‐231 cells, which was blocked by AhR antagonist. Unlike BaP, block of NFAT with CsA inhibited cell migration and cell invasion. In these cells, BaP significantly reduced AhR expression while this reduction was reversed by CH‐223191; however, CsA treatment lowered the AhR expression only at low dose. The level of β4 integrin was significantly reduced by CsA at 1 and 2.5 μm. Protein levels of Snail and TGF‐β receptor 1 were not significantly altered by BaP and CsA treatments. Considering these findings, the low AhR expression and high β4 integrin level following BaP and/or CsA treatments may contribute to the higher invasion/migration in MDA‐MB‐231 cells.

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An EGFR/Src-dependent β4 integrin/FAK complex contributes to malignancy of breast cancer

Cited by 50 publications

References 37 publications

Activation of focal adhesion kinase through an interaction with β4 integrin contributes to tumorigenicity of colon cancer

Activation of focal adhesion kinase through an interaction with β4 integrin contributes to tumorigenicity of colon cancer

ITGB4 deficiency induces senescence of airway epithelial cells through p53 activation

Invasion and migration of MDA‐MB‐231 cells are inhibited by block of AhR and NFAT: role of AhR/NFAT1/β4 integrin signaling

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