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

  • Cell Death Discov. 2023 Jan 25;9(1):30. doi: 10.1038/s41420-023-01319-y.
Lina Wei  1  2 ,  Xiaohong Ma  2  3 ,  Yixin Hou  1  2 ,  Tianyi Zhao  1  2 ,  Rui Sun  1  2 ,  Chunping Qiu  1 ,  Yao Liu  1  2 ,  Ziyi Qiu  1  2 ,  Zhiming Liu  4 ,  Jie Jiang  5
Affiliations
  • 1. Department of Gynecology and Obstetrics, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, 250012, Jinan, Shandong, China.
  • 2. Gynecology Oncology Key Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong, China.
  • 3. Department of Gynecology and Obstetrics, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, 20 Yuhuangding East Road, 264000, Yantai, Shandong, China.
  • 4. Department of Gynecology and Obstetrics, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, 250012, Jinan, Shandong, China. [email protected].
  • 5. Department of Gynecology and Obstetrics, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, 250012, Jinan, Shandong, China. [email protected].
PMID: 36693834 DOI: 10.1038/s41420-023-01319-y
Abstract

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.

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