Chemoresistant ovarian cancer enhances its migration abilities by increasing store-operated Ca2+ entry-mediated turnover of focal adhesions

Huang, Ho Kai; Lin, Yi Hsin; Chang, Heng; Lai, Yi-Sheng; Chen, Ying‐Chi; Huang, Shih-Chang; Chou, Cheng Yang; Chiu, Wen Tai

doi:10.1186/s12929-020-00630-5

Cited by 32 publications

(29 citation statements)

References 66 publications

(71 reference statements)

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“…A study [ 61 ] showed that blocking store-operated Ca 2+ influx (SOCE) in MDA-MB-231 cells resulted in different localization of vinculin that caused slow focal adhesion turnover rate and strong cell adherence. Similarly, another study on mesenchymal-like chemoresistant IGROV1 ovarian cancer cells showed enhanced cell migration as a result of enhanced focal adhesion turnover mediated by SOCE [ 62 ]. It has been suggested that PMCA4b has the ability to decrease near-membrane Ca 2+ concentration in response to SOCE [ 63 ] that may explain, at least partly, the enhanced focal adhesion and reduced motility of the PMCA4b expressing melanoma cells.…”

Section: Discussionmentioning

confidence: 99%

The Plasma Membrane Ca2+ Pump PMCA4b Regulates Melanoma Cell Migration through Remodeling of the Actin Cytoskeleton

Naffa

Padányi

Ignácz

et al. 2021

Cancers

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We demonstrated that the plasma membrane Ca2+ ATPase PMCA4b inhibits migration and metastatic activity of BRAF mutant melanoma cells. Actin dynamics are essential for cells to move, invade and metastasize, therefore, we hypothesized that PMCA4b affected cell migration through remodeling of the actin cytoskeleton. We found that expression of PMCA4b in A375 BRAF mutant melanoma cells induced a profound change in cell shape, cell culture morphology, and displayed a polarized migratory character. Along with these changes the cells became more rounded with increased cell–cell connections, lamellipodia and stress fiber formation. Silencing PMCA4b in MCF-7 breast cancer cells had a similar effect, resulting in a dramatic loss of stress fibers. In addition, the PMCA4b expressing A375 cells maintained front-to-rear Ca2+ concentration gradient with the actin severing protein cofilin localizing to the lamellipodia, and preserved the integrity of the actin cytoskeleton from a destructive Ca2+ overload. We showed that both PMCA4b activity and trafficking were essential for the observed morphology and motility changes. In conclusion, our data suggest that PMCA4b plays a critical role in adopting front-to-rear polarity in a normally spindle-shaped cell type through F-actin rearrangement resulting in a less aggressive melanoma cell phenotype.

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Section: Discussionmentioning

confidence: 99%

The Plasma Membrane Ca2+ Pump PMCA4b Regulates Melanoma Cell Migration through Remodeling of the Actin Cytoskeleton

Naffa

Padányi

Ignácz

et al. 2021

Cancers

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“…Investigation of the contribution of talin to cancer progression is timely. During this study ~ 670 more cancer-associated talin-1 point mutations have been added to the COSMIC database ( Supplementary Fig.S1) and there are recent studies discussing the connection between talin and cancer 23,[55][56][57][58] . The work we present here demonstrates an efficient and fast pipeline approach using bioinformatics tools to characterise future talin mutations identified in cancer and other diseases.…”

Section: Discussionmentioning

confidence: 99%

Cancer associated talin point mutations disorganise cell adhesion and migration

Azizi

Cowell

Mykuliak

et al. 2021

Sci Rep

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Talin-1 is a key component of the multiprotein adhesion complexes which mediate cell migration, adhesion and integrin signalling and has been linked to cancer in several studies. We analysed talin-1 mutations reported in the Catalogue of Somatic Mutations in Cancer database and developed a bioinformatics pipeline to predict the severity of each mutation. These predictions were then assessed using biochemistry and cell biology experiments. With this approach we were able to identify several talin-1 mutations affecting integrin activity, actin recruitment and Deleted in Liver Cancer 1 localization. We explored potential changes in talin-1 signalling responses by assessing impact on migration, invasion and proliferation. Altogether, this study describes a pipeline approach of experiments for crude characterization of talin-1 mutants in order to evaluate their functional effects and potential pathogenicity. Our findings suggest that cancer related point mutations in talin-1 can affect cell behaviour and so may contribute to cancer progression.

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“…there are recent studies discussing the connection between talin and cancer 23,[55][56][57][58] . The work we present here demonstrates an efficient and fast pipeline approach using bioinformatics tools to characterise future talin mutations identified in cancer and other diseases.…”

Section: Discussionmentioning

confidence: 99%

“…Investigation of the contribution of talin to cancer progression is timely. During this study ~670 more cancer–associated talin–1 point mutations have been added to the COSMIC database (Fig.S1) and there are recent studies discussing the connection between talin and cancer 23, 55–58 . The work we present here demonstrates an efficient and fast pipeline approach using bioinformatics tools to characterise future talin mutations identified in cancer and other diseases.…”

Section: Discussionmentioning

confidence: 99%

Cancer associated talin point mutations disorganise cell adhesion and migration

Azizi

Cowell

Mykuliak

et al. 2020

Preprint

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Talin-1 is a key component of the multiprotein adhesion complexes which mediate cell migration, adhesion and integrin signalling and has been linked to cancer in several studies. In this study we analysed mutations in talin-1 reported in the Catalogue of Somatic Mutations in Cancer. A total of 11 talin mutants were selected and expressed in talin-deficient fibroblasts and their functional and structural effects were characterised in detail. An I392N point mutation in the F3 domain caused a three-fold increase in invasion, and enhanced migration compared to wildtype talin. Mutations R1368W and L1539P in the R7 and R8 domains caused increased invasion and proliferation and affected talin-vinculin complexation, but were not linked to changes in their binding affinities with known substrates KANK1 and RIAM measured for isolated talin domains. Lastly, L2509P, a mutation in the dimerisation domain of talin, prevented talin dimer formation, actin recruitment and FAKpTyr397 activation leading to anisotropic cell spreading and loss of random migration. Altogether, this study suggests that cancer derived point mutations in talin-1 can drastically affect cell behaviour and so may contribute to cancer progression. , I. L. et al. (2015). Vinculin controls talin engagement with the actomyosin machinery. Nat. Commun. 6, 10038. (2017). Downregulation of Talin1 promotes hepatocellular carcinoma progression through activation of the ERK1/2 pathway. Leinonen, R., Shumway, M. et al. (2012). The 1000 genomes project: Data management and community access. Nat. Methods 9, 459-462. (2009). Stretching single talin rod molecules activates vinculin binding. Science 323, 638-641. Dupont, S., Morsut, L., Aragona, M., Enzo, E., Giulitti, S., Cordenonsi, M., Zanconato, F., Le Digabel, J., Forcato, M., Bicciato, S. et al. (2011). Role of YAP/TAZ in mechanotransduction. Nature 474, 179-183. Kim, N. G. and Gumbiner, B. M. (2015). Adhesion to fibronectin regulates hippo signaling via the FAK-src-PI3K pathway. A. R. et al. (2010). Studies on the morphology and spreading of human endothelial cells define key inter-and intramolecular interactions for talin1. Eur. J. Cell Biol. 89, 661-673. . (2016). Talin tension sensor reveals novel features of focal adhesion force transmission and mechanosensitivity. Guichard, S. et al. (2016). Rho-associated kinase (ROCK) function is essential for cell cycle progression, senescence and tumorigenesis. Elife 5, e12994. . (2011). Talin-1 overexpression defines high risk foraggressive oral squamous cell carcinoma and promotes cancer metastasis. . (2010). Improved side-chain torsion potentials for the amber ff99SB protein force field.Proteins 78, 1950-1958.

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Chemoresistant ovarian cancer enhances its migration abilities by increasing store-operated Ca2+ entry-mediated turnover of focal adhesions

Cited by 32 publications

References 66 publications

The Plasma Membrane Ca2+ Pump PMCA4b Regulates Melanoma Cell Migration through Remodeling of the Actin Cytoskeleton

The Plasma Membrane Ca2+ Pump PMCA4b Regulates Melanoma Cell Migration through Remodeling of the Actin Cytoskeleton

Cancer associated talin point mutations disorganise cell adhesion and migration

Cancer associated talin point mutations disorganise cell adhesion and migration

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