A SUMOylation-dependent HIF-1α/CLDN6 negative feedback mitigates hypoxia-induced breast cancer metastasis.

ABSTRACT:

Background

We have previously described CLDN6 as a tumor suppressor gene in breast cancer. Here, a new finding is that CLDN6 was upregulated under hypoxia, a commonly recognized factor that promotes tumor metastasis. In this study, we aim to explain this confusing finding and delineate the role of CLDN6 in the breast cancer metastasis induced by hypoxia.

Methods

RNAi and ChIP assays were used to confirm that CLDN6 is transcriptional regulated by HIF-1α. mRNA seq and KEGG analysis were performed to define the downstream pathways of CLDN6. The roles of the CLDN6/SENP1/HIF-1α signaling on tumor metastasis were evaluated by function experiments and clinical samples. Finally, the possible transcription factor of SENP1 was suspected and then validated by ChIP assay.

Results

SUBMITTER: Jia Y 

PROVIDER: S-EPMC7038627 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature