J Cancer 2016; 7(7):768-773. doi:10.7150/jca.13894 This issue

Research Paper

HOXC9 Induces Phenotypic Switching between Proliferation and Invasion in Breast Cancer Cells

Ho Hur*1, Ji-Yeon Lee*2, Seoyeon Yang2, Jie Min Kim2, Anna E. Park2, Myoung Hee Kim2✉

1. Department of Surgery, National Health Insurance Service Ilsan Hospital, Goyang 410-719, Korea;
2. Department of Anatomy, Embryology Laboratory, and Brain Korea 21 PLUS project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
*These authors contributed equally to this work.

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Hur H, Lee JY, Yang S, Kim JM, Park AE, Kim MH. HOXC9 Induces Phenotypic Switching between Proliferation and Invasion in Breast Cancer Cells. J Cancer 2016; 7(7):768-773. doi:10.7150/jca.13894. Available from https://www.jcancer.org/v07p0768.htm

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HOX genes encode a family of transcriptional regulators that are involved in pattern formation and organogenesis during embryo development. In addition, these genes play important roles in adult tissues and some of the dysregulated HOX genes are associated with cancer development and metastasis. Like many other HOX genes, HOXC9 is aberrantly expressed in certain breast cancer cell lines and tissues; however, its specific functions in breast cancer progression were not investigated. In the present study, we demonstrated that HOXC9 overexpression in breast cancer cell lines such as MDA-MB-231 and MCF7 increased the invasiveness but reduced the proliferation of cells, resembling a phenotype switch from a proliferative to an invasive state. Furthermore, the reciprocal result was detected in MCF7 and BT474 cells when the expression level of HOXC9 was reduced with siRNA. The clinical impact of HOXC9 in breast cancer was interpreted from the survival analysis data, in which high HOXC9 expression led to considerably poorer disease-free survival and distant metastasis-free survival, especially in lymph node-positive patients. Together, the prognostic relevance of HOXC9 and the HOXC9-derived phenotypic switch between proliferative and invasive states in the breast cancer cell lines suggest that HOXC9 could be a prognostic marker in breast cancer patients with lymph node metastasis and a target for therapeutic intervention in malignant breast cancer.

Keywords: HOXC9, breast cancer, metastasis, proliferation, invasion.