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Scaffold Protein RACK1 inhibitor compounds prevent the Focal Adhesion Kinase mediated breast cancer cell migration and invasion potential

Ullah, H.; Ahsan, N.; Dakshanamurthy, S.

2021-06-14 cancer biology
10.1101/2021.06.13.448244 bioRxiv
Show abstract

Scaffold protein RACK1 mediates cancer cell migration mostly through regulation of focal adhesion (FA) assembly by promoting a focal adhesion kinase (FAK) activation downstream of the integrin clustering and adhesion at the extracellular matrix (ECM). Here we demonstrated the efficacy of our recently developed RACK1 Y246 phosphorylation inhibitor compounds (SD29 and SD29-14) to inhibit the migration and invasion of MCF7 and MDA-MB-231 breast cancer cell lines. Using multiple assays, our results confirmed that inhibitor compounds effectively prevent the filopodia/lamellipodia development and inhibits the migration of breast cancer cells. A mechanistic model of the inhibitor compounds has been developed. Migration and invasion capabilities of the cancer cells define the metastasis of cancer. Thus, our results suggest a potential therapeutic mechanism of the inhibitors to prevent metastasis in diverse cancers.

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