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CDK5 inhibition abrogates TNBC stem-cell property and enhances anti-PD-1 therapy

ABSTRACT: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that shows high infiltration of cancer stem cells (CSCs), which correlates with poor clinical outcome. Here, we have demonstrated that an aberrant activation of CDK5/pho-PPARg axis associated with TNBC progression closely. CDK5 blockade sufficiently abrogates stemness transformation of TNBC cells, resulting in a significant inhibition of tumor metastatic progression. Moreover, CDK5 inhibitor Rosc attenuates CD44v+ BCSCs, hereby reversing immunosuppressive microenvironment and enhancing anti-PD-1 effects on TNBC. Mechanistically, CDK5/pho-PPARgaxis modulates the ESRP1 degradation via E3 ligase-like activity, leading to CD44 variant (CD44v) expression. Our finding indicates that CDK5 blockade could be a potent strategy to target CSCs in TNBC, and to increase the response to PD-1 blockade in TNBC therapy.

ORGANISM(S): Mus musculus

PROVIDER: GSE132902 | GEO | 2022/06/18

REPOSITORIES: GEO

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CDK5 inhibition abrogates TNBC stem-cell property and enhances anti-PD-1 therapy

Project description:CDK5 inhibition abrogates TNBC stem-cell property and enhances anti-PD-1 therapy

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Use of the dTAG system in vivo to degrade CDK2 and CDK5 in adult mice and explore potential safety liabilities [Duodenum]

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