Talin1 Ser425 phosphorylation promotes colorectal cancer progression and metastasis.

Background: Talin1 serves as a crucial element within the multiprotein adhesion complexes that facilitate processes such as cell migration, adhesion, and integrin signaling. This study aimed to explore the underlying role of Talin1 Ser425 phosphorylation in the development of colorectal cancer (CRC). Methods: Blank plasmids, non-phosphorylatable mutant Talin1 S425A plasmids, and phosphorylation-mimetic mutant Talin1 S425D plasmids were constructed and used for transfection of CRC cells. The expression of mRNA and protein in CRC cells or tumor tissues was assessed by The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and UALCAN databases, immunohistochemistry (IHC), and Western blot (WB). Cell proliferation was assessed via 5-ethynyl-2-deoxyuridine (EDU) proliferation assay and colony formation assay. Cell migration and invasion were detected by wound healing assay and transwell assay. Cell apoptosis was assessed by flow cytometry. The Kaplan-Meier Plotter was used to evaluate the prognostic value of mRNA in CRC. Results: TLN1 was markedly downregulated in CRC tissues while the level of Talin1 Ser425 phosphorylation in CRC tissues and aggressive CRC cells was relatively higher. The S425A mutant inhibited CRC cell proliferation, migration, and invasion, whereas the S425D mutant promoted these processes. Flow cytometry assay showed that cell apoptosis was induced by S425A mutant and suppressed by S425D mutant in RKO cells. Further investigation suggested that CDK5 might be responsible for Talin1 phosphorylation. Conclusions: Talin1 Ser425 phosphorylation is of great importance in CRC development and Talin1 is supposed to be a potential tumor marker and therapeutic target for CRC.