Frizzled 6 endows high‐grade serous ovarian cancer with stem‐like properties and chemoresistance

Author:

Chen Shaorong1,Yang Guang2,Shi Qirong1,Wan Ningning3,Lin Ruyin1,Wang Lianhua1,Hu Xinxin1,Zhuang Xuanxuan1,Yu Liying4,Sui Ming1

Affiliation:

1. Department of Obstetrics and Gynecology The Second Affiliated Hospital of Fujian Medical University Quanzhou China

2. Department of Neurosurgery The Second Affiliated Hospital of Fujian Medical University Quanzhou China

3. Department of Thyroid and Breast Surgery The Second Affiliated Hospital of Fujian Medical University Quanzhou China

4. Central Laboratory The Second Affiliated Hospital of Fujian Medical University Quanzhou China

Abstract

AbstractStem‐like properties contribute to tumor growth, metastasis, and chemoresistance. High‐grade serous ovarian cancer (HGSOC) exhibits a very aggressive phenotype characterized by extensive metastasis, rapid progression, and therapy resistance. Frizzled 6 (FZD6) is overexpressed in HGSOC, and higher levels of FZD6 have been associated with shorter survival times in patients with HGSOC. Functionally, FZD6 promotes HGSOC growth and peritoneal metastasis. It endues HGSOC cells with stem‐like properties by modulating POU5F1, ALDH1, and EPCAM. It can also desensitize HGSOC cells to certain chemical drugs. As a putative ligand for FZD6, WNT7B is also implicated in cell proliferation, stem‐like properties, invasion and migration, and chemoresistance. SMAD7 is a downstream component of FZD6 signaling that is thought to mediate FZD6‐associated phenotypes, at least in part. Therefore, FZD6/WNT7B‐SMAD7 can be considered a tumor‐promoting signaling pathway in HGSOC that may be responsible for tumor growth, peritoneal metastasis, and chemoresistance.

Publisher

Wiley

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