Verteporfin reverses progestin resistance through YAP/TAZ-PI3K-Akt pathway in endometrial carcinoma

Progestin resistance is a problem for patients with endometrial carcinoma (EC) who require conservative treatment with progestin, and its underlying mechanisms remain unclear. YAP and TAZ (YAP/TAZ), downstream transcription coactivators of Hippo pathway, promote viability, metastasis and also drug r...

Full description

Saved in:
Bibliographic Details
Published in:Cell death discovery 2023-01, Vol.9 (1), p.30-30, Article 30
Main Authors: Wei, Lina, Ma, Xiaohong, Hou, Yixin, Zhao, Tianyi, Sun, Rui, Qiu, Chunping, Liu, Yao, Qiu, Ziyi, Liu, Zhiming, Jiang, Jie
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
631/67/1059/2326
631/67/2195
AKT protein
Apoptosis
Biochemistry
Biomedical and Life Sciences
Carcinoma
Cell Biology
Cell Cycle Analysis
Cell migration
Cell proliferation
Cell viability
Drug resistance
Endometrial cancer
Endometrium
Life Sciences
Metastases
Metastasis
Progestin
Stem Cells
Uterine cancer
Yes-associated protein
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Progestin resistance is a problem for patients with endometrial carcinoma (EC) who require conservative treatment with progestin, and its underlying mechanisms remain unclear. YAP and TAZ (YAP/TAZ), downstream transcription coactivators of Hippo pathway, promote viability, metastasis and also drug resistance of malignant tumors. According to our microarray analysis, YAP/TAZ were upregulated in progestin resistant IshikawaPR cell versus progestin sensitive Ishikawa cell, which implied that YAP/TAZ may be a vital promotor of resistance to progestin. We found YAP/TAZ had higher expression levels among the resistant tissues than sensitive tissues. In addition, knocking down YAP/TAZ decreased cell viability, inhibited cell migration and invasion and increased the sensitivity of IshikawaPR cell to progestin. On the contrary, overexpression of YAP/TAZ increased cell proliferation, metastasis and promoted progestin resistance. We also confirmed YAP/TAZ were involved in progestin resistant process by regulating PI3K-Akt pathway. Furthermore, Verteporfin as an inhibitor of YAP/TAZ could increase sensitivity of IshikawaPR cells to progestin in vivo and in vitro. Our study for the first time indicated that YAP/TAZ play an important role in progestin resistance by regulating PI3K-Akt pathway in EC, which may provide ideas for clinical targeted therapy of progestin resistance.
ISSN:2058-7716
2058-7716
DOI:10.1038/s41420-023-01319-y