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CD166 Promotes the Cancer Stem-like Properties of Primary Epithelial Ovarian Cancer Cells
Dae Kyoung Kim1 (Post-doctoral fellow), Min Hee Ham1 (Graduate student), Seo Yul Lee1 (Graduate student), Min Joo Shin1 (Graduate student), Ye Eun Kim1 (Graduate student), Parkyong Song2 (Professor), Dong-Soo Suh3 (Professor), Jae Ho Kim 1,4,* (Professor)
1Department of Physiology and 2Department of Convergence Medicine and 3Department of Obstetrics and Gynecology, Pusan National University School of Medicine,
44Research Institute of Convergence Biomedical Science and Technology, Pusan National University Yangsan Hospital
Abstract
Cancer stem cells (CSCs) or tumor-initiating cells are thought to play critical roles in tumorigenesis, metastasis, drug resistance, and tumor recurrence. For the diagnosis and targeted therapy of CSCs, the molecular identity of biomarkers or therapeutic targets for CSCs needs to be clarified. In the present study, we identified CD166 as a novel marker expressed in the sphere-forming CSC population of A2780 epithelial ovarian cancer cells and primary ovarian cancer cells. The CD166+ cells isolated from A2780 cells and primary ovarian cancer cells highly expressed CSC markers including ALDH1a1, OCT4, and SOX2, and ABC transporters which are implicated in drug resistant properties of CSCs. The CD166+ cells exhibited enhanced CSC-like properties, such as increased sphere-forming ability, cell migration and adhesion abilities, resistance to conventional anti-cancer drugs, and high tumorigenic potential in a xenograft mouse model. Knockdown of CD166 expression in the sphere-forming ovarian CSCs abrogated their CSC-like properties. Moreover, silencing of CD166 expression in the sphere-forming CSCs suppressed the phosphorylation of focal adhesion kinase, paxillin, and SRC. These results suggest that CD166 plays a key role in the regulation of CSC-like properties and focal adhesion kinase signaling in ovarian cancer.
Abstract, Accepted Manuscript(in press) [Submitted on May 13, 2020, Accepted on June 8, 2020]
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