Cdh1-mediated Skp2 degradation by dioscin reprogrammes aerobic glycolysis and inhibits colorectal cancer cells growth.

ABSTRACT:

Background

The F-box protein S-phase kinase-associated protein 2 (Skp2) is overexpressed and correlated with poor prognosis in human malignancies, including colorectal cancer (CRC).

Methods

A natural product library was used for natural compound screening through glycolysis analysis. The expression of Skp2 in CRCs and the inhibitory effect of dioscin on glycolysis were examined through methods of immunoblot, immunofluorescence, immunohistochemical staining, anchorage-dependent and -independent growth assays, EdU incorporation assay, ubiquitination analysis, co-immunoprecipitation assay, CRISPR-Cas9-based gene knockout, and xenograft experiment.

Findings

We demonstrated that Skp2 was highly expressed in CRC tissues and cell lines. Knockout of Skp2 inhibited HK2 and gly

SUBMITTER: Zhou L 

PROVIDER: S-EPMC7000337 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature