American Association for Cancer Research
21598290cd120388-sup-supplementary_figure_6_pdf_file_-_141k.pdf (141.2 kB)

Supplementary Figure 6 from RHOA-FAK Is a Required Signaling Axis for the Maintenance of KRAS-Driven Lung Adenocarcinomas

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journal contribution
posted on 2023-04-03, 20:47 authored by Georgia Konstantinidou, Giorgio Ramadori, Francesca Torti, Kim Kangasniemi, Rachel E. Ramirez, Yiran Cai, Carmen Behrens, Michael T. Dellinger, Rolf A. Brekken, Ignacio I. Wistuba, Adriana Heguy, Julie Teruya-Feldstein, Pier Paolo Scaglioni

Supplementary Figure 6 PDF file - 141K, This Figure shows that FAK is co-expressed with RHOA in lung adenocarcinomas. In addition, we provide the validation of RHOA-GTP antibody on human specimens by IHC



Non–small cell lung cancer (NSCLC) often expresses mutant KRAS together with tumor-associated mutations of the CDKN2A locus, which are associated with aggressive, therapy-resistant tumors. Here, we unravel specific requirements for the maintenance of NSCLC that carries this genotype. We establish that the extracellular signal-regulated kinase (ERK)/RHOA/focal adhesion kinase (FAK) network is deregulated in high-grade lung tumors. Suppression of RHOA or FAK induces cell death selectively in mutant KRAS;INK4A/ARF-deficient lung cancer cells. Furthermore, pharmacologic inhibition of FAK caused tumor regression specifically in the high-grade lung cancer that developed in mutant Kras;Cdkn2a-null mice. These findings provide a rationale for the rapid implementation of genotype-specific targeted therapies using FAK inhibitors in patients with cancer.Significance: Targeted therapies are effective for only a small fraction of patients with cancer. We report that FAK inhibitors exert potent antitumor effects in NSCLCs that express mutant KRAS in association with INK4A/ARF deficiency. These results reveal a novel genotype-specific vulnerability of cancer cells that can be exploited for therapeutic purposes. Cancer Discov; 3(4); 444–57. ©2013 AACR.This article is highlighted in the In This Issue feature, p. 363

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