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FARP1 boosts CDC42 activity from integrin ?v?5 signaling and correlates with poor prognosis of advanced gastric cancer.

ABSTRACT: Considering the poor prognosis of most advanced cancers, prevention of invasion and metastasis is essential for disease control. Ras homologous (Rho) guanine exchange factors (GEFs) and their signaling cascade could be potential therapeutic targets in advanced cancers. We conducted in silico analyses of The Cancer Genome Atlas expression data to identify candidate Rho-GEF genes showing aberrant expression in advanced gastric cancer and found FERM, Rho/ArhGEF, and pleckstrin domain protein 1 (FARP1) expression is related to poor prognosis. Analyses in 91 clinical advanced gastric cancers of the relationship of prognosis and pathological factors with immunohistochemical expression of FARP1 indicated that high expression of FARP1 is significantly associated with lymphatic invasion, lymph metastasis, and poor prognosis of the patients (P?=?0.025). In gastric cancer cells, FARP1 knockdown decreased cell motility, whereas FARP1 overexpression promoted cell motility and filopodium formation via CDC42 activation. FARP1 interacted with integrin ?5, and a potent integrin ?v?5 inhibitor (SB273005) prevented cell motility in only high FARP1-expressing gastric cancer cells. These results suggest that the integrin ?v?5-FARP1-CDC42 axis plays a crucial role in gastric cancer cell migration and invasion. Thus, regulatory cascade upstream of Rho can be a specific and promising target of advanced cancer treatment.

SUBMITTER: Hirano T

PROVIDER: S-EPMC7005035 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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FARP1 boosts CDC42 activity from integrin αvβ5 signaling and correlates with poor prognosis of advanced gastric cancer.

Hirano Takuro T Shinsato Yoshinari Y Tanabe Kan K Higa Nayuta N Kamil Muhammad M Kawahara Kohichi K Yamamoto Masatatsu M Minami Kentaro K Shimokawa Michiko M Arigami Takaaki T Yanagita Shigehiro S Matushita Daisuke D Uenosono Yoshikazu Y Ishigami Sumiya S Kijima Yuko Y Maemura Kosei K Kitazono Ikumi I Tanimoto Akihide A Furukawa Tatsuhiko T Natsugoe Shoji S

Oncogenesis 20200206 2

Considering the poor prognosis of most advanced cancers, prevention of invasion and metastasis is essential for disease control. Ras homologous (Rho) guanine exchange factors (GEFs) and their signaling cascade could be potential therapeutic targets in advanced cancers. We conducted in silico analyses of The Cancer Genome Atlas expression data to identify candidate Rho-GEF genes showing aberrant expression in advanced gastric cancer and found FERM, Rho/ArhGEF, and pleckstrin domain protein 1 (FAR ...[more]

PMID: 32029704

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FARP1 boosts CDC42 activity from integrin ?v?5 signaling and correlates with poor prognosis of advanced gastric cancer.

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FARP1 boosts CDC42 activity from integrin αvβ5 signaling and correlates with poor prognosis of advanced gastric cancer.

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