Essential role of PLD2 in hypoxia-induced stemness and therapy resistance in ovarian tumors.

ABSTRACT:

Background

Hypoxia in solid tumors is an important source of chemoresistance that can determine poor patient prognosis. Such chemoresistance relies on the presence of cancer stem cells (CSCs), and hypoxia promotes their generation through transcriptional activation by HIF transcription factors.

Methods

We used ovarian cancer (OC) cell lines, xenograft models, OC patient samples, transcriptional databases, induced pluripotent stem cells (iPSCs) and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq).

Results

Here, we show that hypoxia induces CSC formation and chemoresistance in ovarian cancer through transcriptional activation of the PLD2 gene. Mechanistically, HIF-1α activates PLD2 transcription through hypoxia response elements, and both hypoxia a

SUBMITTER: Munoz-Galvan S 

PROVIDER: S-EPMC10895852 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature