PVT1 is a stress-responsive lncRNA that drives ovarian cancer metastasis and chemoresistance

Metastatic growth of ovarian cancer cells into the peritoneal cavity requires adaptation to various cellular stress factors to facilitate cell survival and growth. Here, we demonstrate the role of PVT1, one such stress induced long non-coding RNA, in ovarian cancer growth and metastasis. PVT1 is an amplified and overexpressed lncRNA in ovarian cancer with strong predictive value for survival and response to targeted therapeutics. We find that expression of PVT1 is regulated by tumor cells in response to
cellular stress, particularly loss of cell–cell contacts and changes in matrix rigidity occurring in a YAP1-dependent manner. Induction
of PVT1 promotes tumor cell survival, growth, and
migration. Conversely, reducing PVT1 levels robustly abrogates
metastatic behavior and tumor cell dissemination in cell lines and
syngeneic transplantation models in vivo. We find that reducing
PVT1 causes widespread changes in the transcriptome leading to
alterations in cellular stress response and metabolic pathways
including doxorubicin metabolism, which impacts chemosensitivity.
Together, these findings implicate PVT1 as a promising therapeutic
target to suppress metastasis and chemoresistance in
ovarian cancer.