The CDK6-c-Jun-Sp1-MMP-2 axis as a biomarker and therapeutic target for triple-negative breast cancer.

ABSTRACT: Triple-negative breast cancer (TNBC) has high metastatic, drug-resistance, and recurrence rates, and is characterized by an angiogenic and fibrotic microenvironment that favors cancer malignancy. However, details of the mechanisms underlying malignancy are still largely unknown. Our mouse model indicated that knockdown of CDK6 inhibited lung metastasis significantly compared to parental cells. Immunohistochemical analyses revealed that the levels of collagen and the angiogenic marker matrix metalloproteinase (MMP)-2 were much lower in CDK6-deficient cells. To examine mechanisms in the CDK6-mediated phenotype of cancer cells, we studied its role in MMP-2 expression. CDK6 mediated the recruitment of transcription factors including c-Jun and Sp1 to the MMP2 promoter. Knockdown of CDK6

SUBMITTER: Luo CW 

PROVIDER: S-EPMC7783751 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature