Integrin signaling and lung cancer

Caccavari, Francesca; Valdembri, Donatella; Sandri, Chiara; Bussolino, Federico; Serini, Guido

doi:10.4161/cam.4.1.10976

Cited by 50 publications

(56 citation statements)

References 66 publications

(74 reference statements)

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“…Integrins are known to play multiple roles in cancer (10,34), and integrins α5β1 and αvβ5 participate in tumor cell adhesion and motility in lung cancer (17,36). We found that high integrin β3 mRNA expression levels in patients with ALK-rearranged NSCLC were Table S4).…”

Section: Discussionmentioning

confidence: 67%

“…With at least 80 clinical trials on the application of integrins ongoing, these proteins have long been the focus of the biotechnology and pharmaceutical industries as potential therapeutic targets, given their central roles in almost all aspects of human biology, as well as in the pathobiology of many diseases (16). In NSCLC, integrin expression has been reported Author Manuscript Published OnlineFirst on May 18, 2018; DOI: 10.1158/1078-0432.CCR- in tumor cells and the cellular matrix, and has been found to accompany angiogenesis (17).…”

Section: Introductionmentioning

confidence: 99%

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Integrin β3 Inhibition Enhances the Antitumor Activity of ALK Inhibitor in ALK-Rearranged NSCLC

Noh

Sohn

Song

et al. 2018

Clinical Cancer Research

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Purpose: Anaplastic lymphoma kinase (ALK)-positive cancers are sensitive to small-molecule ALK kinase inhibitors, but most cases experience failure following treatment. Hence, additional drug targets and combination therapeutic treatments are needed. We investigated gene expression that is regulated by the expression of ALK and explored its roles in cancer progression and therapeutic implication. Experimental Design: We screened ALK-rearranged non–small cell lung cancer (NSCLC) cases using immunohistochemistry and fluorescence in situ hybridization and then conducted multiplex gene expression analysis. We also performed a clinicopathologic analysis to validate the findings. Additional cellular experiments, including inhibition and migration assays, and in vivo lung cancer model studies were performed. Results: Among patients with ALK-rearranged NSCLC, integrin β3 (ITGB3) was one of the overexpressed genes in comparison with that in ALK-negative NSCLC (P = 0.0003). ALK and integrin β3 expression were positively correlated, and we discovered that high integrin β3 mRNA expression was associated with metastasis and more advanced tumor stages (P < 0.005; P < 0.05). Furthermore, we found that inhibition of both ALK and integrin β3 led to increased drug sensitivity in vitro and in vivo (both P < 0.05). Conclusions: We discovered a positive correlation between ALK and integrin β3 expression levels in ALK-rearranged NSCLC. Our findings suggest that high integrin β3 expression in ALK-rearranged NSCLC is associated with tumor progression and a worse prognosis. This finding demonstrates the prognostic value of integrin β3 and provides a rationale for combination treatment with ALK and integrin β3 inhibitors in patients with ALK-rearranged NSCLC. Clin Cancer Res; 24(17); 4162–74. ©2018 AACR.

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Section: Discussionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Integrin β3 Inhibition Enhances the Antitumor Activity of ALK Inhibitor in ALK-Rearranged NSCLC

Noh

Sohn

Song

et al. 2018

Clinical Cancer Research

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“…Alternately, ECM can be stiffened by increased matrix production and deposition of collagen via Lysyl Oxidase (LOX) signaling (Gao et al, 2010). For instance, ECM accumulation by increased Collagen deposition has been documented in many tumor cell types, including glioma, breast, and lung cancers (Huijbers et al, et al;Caccavari et al, 2010). This abnormal ECM function can cause changes in the mechano-transduction pathways that regulate growth and migration pathways.…”

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confidence: 99%

“…MAPK signaling is highly affected in cancer that activates many downstream applications. Similarly, focal adhesions are the point of cell-ECM matrix interaction and are comprised of integrins that cluster together and bind the ECM, thus triggering downstream pathways mediated through Focal Adhesion Kinase (FAK) (Caccavari et al, 2010). These downstream signaling pathways have the ability to modulate MMP and tissue inhibitors of metalloproteases (TIMP) that can adjust ECM synthesis and degradation (Caccavari et al, 2010).…”

mentioning

confidence: 99%

“…Similarly, focal adhesions are the point of cell-ECM matrix interaction and are comprised of integrins that cluster together and bind the ECM, thus triggering downstream pathways mediated through Focal Adhesion Kinase (FAK) (Caccavari et al, 2010). These downstream signaling pathways have the ability to modulate MMP and tissue inhibitors of metalloproteases (TIMP) that can adjust ECM synthesis and degradation (Caccavari et al, 2010). It is now evident that there exists a complex feedback mechanism between cancer cells and ECM that influences the fate of the tumor (Blaauboer et al, 2014).…”

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confidence: 99%

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