KIF4 enforces the progression of colorectal cancer by inhibiting the autophagy via activating the Hedgehog signaling pathway

This work firstly scrutinized the effect of KIF4 on the progression of CRC. KIF4 expression in CRC clinical tissues and cells was evaluated by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. Cell counting kit-8 assay, Transwell invasion and migratio...

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Veröffentlicht in:Archives of biochemistry and biophysics 2022-11, Vol.731, p.109423-109423, Article 109423
Hauptverfasser: Fu, Yuxiang, Li, Fang, Sun, Xiao, Zhu, Chang, Fan, Baohang, Zhong, Keli
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Sprache:eng
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Zusammenfassung:This work firstly scrutinized the effect of KIF4 on the progression of CRC. KIF4 expression in CRC clinical tissues and cells was evaluated by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. Cell counting kit-8 assay, Transwell invasion and migration assay were implemented to research the function of KIF4 on the proliferation, invasion and migration of CRC cells. The effect of KIF4 on the autophagy and the Hedgehog pathway activityavtivity in CRC cells was explored in the presence or absence of rapamycin and ring propylamine. The expression of autophagy-related proteins was scrutinized by qRT-PCR, Western blot and immunofluorescence. Autophagosomes in CRC cells was observed by transmission electron microscopy. In vivo xenograft experiment was executed. Immunohistochemistry of xenograft tumor tissues was executed to investigate the Hedgehog pathway activityactivtiy. KIF4 was abundantly expressed in CRC clinical tissues and cells. KIF4 enforced the proliferation, invasion, migration of CRC cells, repressed the autophagy and activated the Hedgehog pathway in CRC cells. Rapamycin and ring propylamine treatment reversed the inhibition of KIF4 on the autophagy and the promotion of KIF4 on the Hedgehog pathway activity in CRC cells. Ring propylamine treatment reversed the inhibition of KIF4 on the autophagy in CRC cells. KIF4 intensified the in vivo growth of CRC cells and activated the Hedgehog pathway in xenograft tumor tissues. KIF4 acted as an oncogene in CRC by inhibiting the autophagy via activating the Hedgehog pathway. It might be a potential target for CRC treatment. [Display omitted] •Overexpression of KIF4 was occurred in CRC tissues and cells.•KIF4 enhanced the proliferation, invasion and migration of CRC cells.•KIF4 enforced the proliferation of CRC cells by repressing the autophagy.•KIF4 inhibited the autophagy by activiting the Hedgehog pathway in CRC cells.•KIF4 enforced the growth of CRC cells in vivo.
ISSN:0003-9861
1096-0384
DOI:10.1016/j.abb.2022.109423