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- W3003334393 abstract "Invadopodia formation is a key driver of cancer metastasis. The noncanonical IkB-related kinase IKKe has been implicated in cancer metastasis, but its roles in invadopodia formation and colorectal cancer (CRC) metastasis are unclear. Methods: Immunofluorescence, gelatin-degradation assay, wound healing assay and transwell invasion assay were used to determine the influence of IKKe over-expression, knockdown and pharmacological inhibition on invadopodia formation and the migratory and invasive capacity of CRC cells in vitro. Effects of IKKe knockdown or pharmacological inhibition on CRC metastasis were examined in mice. Immunohistochemistry staining was used to detect expression levels of IKKe in CRC patient tissues, and its association with prognosis in CRC patients was also analyzed. Immunoprecipitation, western blotting and in vitro kinase assay were constructed to investigate the molecular mechanisms. Results: IKKe co-localizes with F-actin and the invadopodia marker Tks5 at the gelatin-degrading sites of CRC cells. Genetic over-expression/knockdown or pharmacological inhibition of IKKe altered invadopodia formation and the migratory and invasive capacity of CRC cells in vitro. In vivo, knockdown or pharmacological inhibition of IKKe significantly suppressed metastasis of CRC cells in mice. IKKe knockdown also inhibited invadopodia formation in vivo. Clinical investigation of tumor specimens from 191 patients with CRC revealed that high IKKe expression correlates with metastasis and poor prognosis of CRC. Mechanistically, IKKe directly binds to and phosphorylates kindlin-2 at serine 159; this effect mediates the IKKe-induced invadopodia formation and promotion of CRC metastasis. Conclusions: We identify IKKe as a novel regulator of invadopodia formation and a unique mechanism by which IKKe promotes the metastasis of CRC. Our study suggests that IKKe is a potential target to suppress CRC metastasis." @default.
- W3003334393 created "2020-02-07" @default.
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- W3003334393 date "2020-01-01" @default.
- W3003334393 modified "2023-10-15" @default.
- W3003334393 title "IKKε phosphorylates kindlin-2 to induce invadopodia formation and promote colorectal cancer metastasis" @default.
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- W3003334393 doi "https://doi.org/10.7150/thno.40397" @default.
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