Talin1 Promotes Tumor Invasion and Metastasis via Focal Adhesion Signaling and Anoikis Resistance

Sakamoto, Shinichi; McCann, Richard O.; Dhir, Rajiv; Kyprianou, Natasha

doi:10.1158/0008-5472.can-09-2833

Cited by 178 publications

(183 citation statements)

References 38 publications

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“…A recent study showed that the regulation of talin levels by overexpression or siRNA silencing greatly affects prostate cancer cell migration and invasion (45). Because we identified talin as an intracellular CtsH target in PC-3 cells, we propose that CtsH could regulate prostate cancer cell migration by cleaving talin.…”

Section: Discussionmentioning

confidence: 81%

Cathepsin H Mediates the Processing of Talin and Regulates Migration of Prostate Cancer Cells

Jevnikar

Rojnik

Jamnik

et al. 2013

Journal of Biological Chemistry

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Background: Cathepsin H (CtsH) is an aminopeptidase that is involved in tumor progression. Results: CtsH cleaves talin, and its inhibition reduces the migration of prostate cancer cells. Conclusion: CtsH affects cell migration by influencing the activity of integrins, a process that could be regulated by talin cleavage. Significance: Identification of novel CtsH proteolytic targets is important to understand and control tumor progression.

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Section: Discussionmentioning

confidence: 81%

Cathepsin H Mediates the Processing of Talin and Regulates Migration of Prostate Cancer Cells

Jevnikar

Rojnik

Jamnik

et al. 2013

Journal of Biological Chemistry

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“…3C). Thus, PHIP can regulate the expression of upstream mediators of the IGF axis and downstream mediators of tumor cell invasion (8).…”

Section: Resultsmentioning

confidence: 99%

“…In addition, microarray analysis revealed down-regulation of Tln1 in melanoma cells with reduced Phip expression. TLN1, which is involved in the assembly of actin filaments, has been shown to mediate tumor invasion and metastasis through AKT-dependent effects (8). in which PHIP directs a coordinated program of melanoma cell invasion through the activation of TLN1 and AKT.…”

Section: Discussionmentioning

confidence: 99%

Pleckstrin homology domain-interacting protein (PHIP) as a marker and mediator of melanoma metastasis

Semir

Nosrati

Bezrookove

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Although melanomas with mutant v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) can now be effectively targeted, there is no molecular target for most melanomas expressing wildtype BRAF. Here, we show that the activation of Pleckstrin homology domain-interacting protein (PHIP), promotes melanoma metastasis, can be used to classify a subset of primary melanomas, and is a prognostic biomarker for melanoma. Systemic, plasmidbased shRNA targeting of Phip inhibited the metastatic progression of melanoma, whereas stable suppression of Phip in melanoma cell lines suppressed metastatic potential and prolonged the survival of tumor-bearing mice. The human PHIP gene resides on 6q14.1, and although 6q loss has been observed in melanoma, the PHIP locus was preserved in melanoma cell lines and patient samples, and its overexpression was an independent adverse predictor of survival in melanoma patients. In addition, a high proportion of PHIP-overexpressing melanomas harbored increased PHIP copy number. PHIP-overexpressing melanomas include tumors with wild-type BRAF, neuroblastoma RAS viral (v-ras) oncogene homolog, and phosphatase and tensin homolog, demonstrating PHIP activation in triple-negative melanoma. These results describe previously unreported roles for PHIP in predicting and promoting melanoma metastasis, and in the molecular classification of melanoma.T he successful development of targeted therapy for melanomas harboring BRAF mutations has garnered significant attention, given the promising results of small molecule inhibitors of mutant BRAF (1). However, the molecular basis underlying the metastasis of the ≈50% of all human melanomas that lack a BRAF mutation, and specific targets for the therapy of these melanomas, is unclear. As a result, "triple-negative melanoma" patients, whose tumors harbor wild-type v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), neuroblastoma RAS viral (vras) oncogene homolog (NRAS), and phosphatase and tensin homolog (PTEN) (the most common mutations observed in melanoma), are not candidates for most targeted therapies developed to date.The type I insulin-like growth factor receptor (IGF1R) signaling pathway has been recognized to play an increasingly important role in tumorigenesis (2, 3). Binding of IGF1 or IGF2 to IGF1R results in phosphorylation of tyrosine and carboxyl-terminal serine residues that form binding sites for the insulin-receptor substrate (IRS) docking proteins. IRS activation results in PI3K recruitment and AKT activation (4). Efficient docking of IRS proteins is mediated via their pleckstrin homology domain. Pleckstrin homology domain-interacting protein (PHIP), initially identified through interactions with the pleckstrin homology domain of IRS proteins, has been shown to mediate transcriptional responses in pancreatic islet cells (5), and is important for postnatal growth (6). Previously, we identified PHIP as the gene most highly overexpressed in metastatic melanomas, compared with primary tumors by cDNA microarray analysis (7). Although PHIP plays a r...

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“…For example, caveolin-1 promotes metastasis of bladder cancer through a pharmacologically tractable common downstream signaling pathway and has been further researched for personalized therapy to suppress metastases (Thomas et al, 2011). Talin1 overexpression enhances cancer cell adhesion, migration, and invasion by activating survival signals and conferring resistance to anoikis (Sakamoto et al, 2010). Other examples are adenylate cyclase-associated protein 1 and human fatty acid synthase (Yamazaki et al, 2009;Shao et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Parallel proteomic analysis in muscle-invasive bladder transitional cell carcinoma and cancer-related stroma

Niu

Qi²,

Liu³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. To bring about improvements in cancer biology research and elucidate mechanism-based therapeutic targets, we studied the proteome expression profile of purified normal urothelial cells (cancer cells) and normal stromal cells (cancerous stromal cells). Based on the expression profile, biomarker discovery and the mechanisms of multistep carcinogenesis were explored. We found that 1412/1403 unique proteins commonly appeared in 4 sets of paired cancer/normal tissue, and 1753 proteins were differentially expressed. Three hundred and forty-one proteins were repeatedly expressed in both cancer and cancer stromal cells; 358 proteins were repeatedly expressed in both normal urothelial and normal stromal cells. Among them, 186/203 proteins were specific repeat expressions in cancer/normal tissue and thought to play an important role in cancer-stroma interactions. Differential proteins were further analyzed using bioinformatic tools and compared with the published literature. GO enrichment/depletion analysis indicated that carcinogenesis involved all the biological processes and all the cellular components. Five hundred and sixty-eight differential proteins were located in the well-known biological Kyoto Encyclopedia of Genes and Genomes pathways, including metabolic pathways, ribosome spliceosome, and endocytosis. One hundred and thirty-nine of the 186 proteins that displayed specific repeat expressions in cancer tissue were located in the biological Kyoto Encyclopedia of Genes and Genomes pathways and are thought to be candidate biomarkers for targeted therapy.

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Talin1 Promotes Tumor Invasion and Metastasis via Focal Adhesion Signaling and Anoikis Resistance

Cited by 178 publications

References 38 publications

Cathepsin H Mediates the Processing of Talin and Regulates Migration of Prostate Cancer Cells

Cathepsin H Mediates the Processing of Talin and Regulates Migration of Prostate Cancer Cells

Pleckstrin homology domain-interacting protein (PHIP) as a marker and mediator of melanoma metastasis

Parallel proteomic analysis in muscle-invasive bladder transitional cell carcinoma and cancer-related stroma

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