YAP/TEAD co-activator regulated pluripotency and chemoresistance in ovarian cancer initiated cells

Yan Xia; Yin-Li Zhang; Chao Yu; Ting Chang; Heng-Yu Fan

doi:10.1371/journal.pone.0109575

YAP/TEAD co-activator regulated pluripotency and chemoresistance in ovarian cancer initiated cells

PLoS One. 2014 Nov 4;9(11):e109575. doi: 10.1371/journal.pone.0109575. eCollection 2014.

Authors

Yan Xia¹, Yin-Li Zhang², Chao Yu², Ting Chang³, Heng-Yu Fan²

Affiliations

¹ Assisted Reproductive Centre, Shaanxi Maternal and Child Care Service Hospital, Xi'an, China; Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou, China.
² Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou, China.
³ Department of Neurology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China.

Abstract

Recent evidence suggests that some solid tumors, including ovarian cancer, contain distinct populations of stem cells that are responsible for tumor initiation, growth, chemo-resistance, and recurrence. The Hippo pathway has attracted considerable attention and some investigators have focused on YAP functions for maintaining stemness and cell differentiation. In this study, we successfully isolated the ovarian cancer initiating cells (OCICs) and demonstrated YAP promoted self-renewal of ovarian cancer initiated cell (OCIC) through its downstream co-activator TEAD. YAP and TEAD families were required for maintaining the expression of specific genes that may be involved in OCICs' stemness and chemoresistance. Taken together, our data first indicate that YAP/TEAD co-activator regulated ovarian cancer initiated cell pluripotency and chemo-resistance. It proposed a new mechanism on the drug resistance in cancer stem cell that Hippo-YAP signal pathway might serve as therapeutic targets for ovarian cancer treatment in clinical.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B / metabolism
Adaptor Proteins, Signal Transducing / antagonists & inhibitors
Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism*
Animals
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use
Cell Line, Tumor
Cell Proliferation
Cell Survival / drug effects
DNA-Binding Proteins / antagonists & inhibitors
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Drug Resistance, Neoplasm / drug effects
Female
Glycogen Synthase Kinase 3 / metabolism
Humans
Mice
Mice, Nude
Mitogen-Activated Protein Kinases / metabolism
Neoplastic Stem Cells / cytology
Neoplastic Stem Cells / metabolism*
Nuclear Proteins / antagonists & inhibitors
Nuclear Proteins / genetics
Nuclear Proteins / metabolism*
Ovarian Neoplasms / drug therapy
Ovarian Neoplasms / metabolism
Ovarian Neoplasms / pathology
Phosphoproteins / antagonists & inhibitors
Phosphoproteins / genetics
Phosphoproteins / metabolism*
RNA Interference
Signal Transduction
TEA Domain Transcription Factors
Transcription Factors / antagonists & inhibitors
Transcription Factors / genetics
Transcription Factors / metabolism*
Transplantation, Heterologous
YAP-Signaling Proteins

Substances

ABCB1 protein, human
ATP Binding Cassette Transporter, Subfamily B
Adaptor Proteins, Signal Transducing
Antineoplastic Agents
DNA-Binding Proteins
Nuclear Proteins
Phosphoproteins
TEA Domain Transcription Factors
TEAD1 protein, human
Transcription Factors
YAP-Signaling Proteins
YAP1 protein, human
Mitogen-Activated Protein Kinases
Glycogen Synthase Kinase 3

Grants and funding

This study was supported by the National Natural Science Foundation of China (81172473, 31371449), the National Basic Research Program of China (2011CB944504, 2012CB944403), and Basic Scientific Research Funding of Zhejiang University (2011QN81001). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.