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IQGAP1 Is Involved in Enhanced Aggressive Behavior of Epithelial Ovarian Cancer Stem Cell-Like Cells During Differentiation
  1. Lu Huang, MD*,
  2. Shanshan Xu, MD*,
  3. Dongxiao Hu, MD*,,
  4. Weiguo Lu, PhD*,,
  5. Xing Xie, PhD*, and
  6. Xiaodong Cheng, MD*,
  1. *Women’s Reproductive Health Laboratory of Zhejiang Province, and
  2. Department of Gynecologic Oncology, Women’s Hospital School of Medicine, Zhejiang University, Hangzhou, China.
  1. Address correspondence and reprint requests to Xiaodong Cheng, MD, Women’s Reproductive Health Laboratory of Zhejiang Province, Department of Gynecologic Oncology, Women’s Hospital, School of Medicine, Zhejiang University, Xueshi Rd #2, Hangzhou, 310006, China. E-mail: chengxd{at}zju.edu.cn.

Abstract

Background Wide metastasis is one of characteristics of ovarian cancer. Cancer stem cells, as a source in cancer invasion and metastasis, possess powerful potential of differentiation. Scaffolding IQ domain GTPase-activating protein 1 (IQGAP1) plays a key role in the invasion and metastasis of cancer cells, but IQGAP1’s role in cancer stem cells including ovarian cancer was unclear.

Methods Spheroid culture with serum-free medium was used for enriching ovarian cancer stem cell-like cells (CSC-LCs) from 3AO cell line, and a medium with 10% fetal bovine serum was used to induce the differentiation of CSC-LCs. Immunofluorescence was for detecting the stem markers OCT4 and SOX2. The quantitative real-time-polymerase chain reaction and Western blotting were performed to determine the messenger RNA and protein expression of IQGAP1, respectively. The capacity of cell invasion was evaluated by transwell chamber assay.

Results Ovarian CSC-LCs obtained through spheroid culture showed irregularly elongated appearance, CD24 negative, and OCT4 and SOX2 positive. IQGAP1 expression was decreased in ovarian CSC-LCs compared with parental 3AO cells, but increased de novo during the differentiation of CSC-LCs. Knockdown of IQGAP1 by specific small interfering RNA remarkably weakened invasion capacity of 2-day differentiated ovarian CSC-LCs.

Conclusions Increased IQGAP1 expression during the differentiation of CSC-LCs is involved in an aggressive cell behavior, which may contribute to metastasis of ovarian cancer.

  • IQGAP1
  • Ovarian cancer
  • Cancer stem cell-like cells
  • Differentiation
  • Invasion

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Footnotes

  • The authors declare no conflicts of interest.

  • Supported by the Zhejiang Provincial Natural Science Foundation of China (grant no. LY12H16024).

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