Septin-2 is overexpressed in epithelial ovarian cancer and mediates proliferation via regulation of cellular metabolic proteins

Nicole E. James; Evelyn Cantillo; Naohiro Yano; Clinton O. Chichester; Paul A. DiSilvestro; Virginia Hovanesian; R. Shyama Prasad Rao; Kyukwang K. Kim; Richard G. Moore; Nagib Ahsan; Jennifer R. Ribeiro

doi:10.18632/oncotarget.26836

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Research Papers:

Septin-2 is overexpressed in epithelial ovarian cancer and mediates proliferation via regulation of cellular metabolic proteins

Nicole E. James, Evelyn Cantillo, Naohiro Yano, Clinton O. Chichester, Paul A. DiSilvestro, Virginia Hovanesian, R. Shyama Prasad Rao, Kyukwang K. Kim, Richard G. Moore, Nagib Ahsan and Jennifer R. Ribeiro

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Oncotarget. 2019; 10:2959-2972. https://doi.org/10.18632/oncotarget.26836

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Abstract

Nicole E. James1^,2, Evelyn Cantillo1, Naohiro Yano3, Clinton O. Chichester2, Paul A. DiSilvestro1^,8, Virginia Hovanesian4, R. Shyama Prasad Rao5, Kyukwang K. Kim6, Richard G. Moore6, Nagib Ahsan7^,8 and Jennifer R. Ribeiro1^,8

1 Division of Gynecologic Oncology, Program in Women’s Oncology, Department of Obstetrics and Gynecology, Women and Infants Hospital, Providence, RI, USA

2 Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, USA

3 Department of Surgery, Roger Williams Medical Center, Boston University Medical School, Providence, RI, USA

4 Core Research Laboratories, Rhode Island Hospital, Providence, RI, USA

5 Biostatistics and Bioinformatics Division, Yenepoya Research Center, Yenepoya University, Mangalore, India

6 Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA

7 Center for Cancer Research Development, Proteomics Core Facility, Rhode Island Hospital, Providence, RI, USA

8 Division of Biology and Medicine, Warren Alpert Medical School, Brown University, Providence, RI, USA

Correspondence to:

Nagib Ahsan,	email:	[email protected]
Jennifer R. Ribeiro,	email:	[email protected]

Keywords: ovarian cancer; proteomics; septin-2; metabolic proteins

Received: December 18, 2018 Accepted: March 23, 2019 Published: April 26, 2019

ABSTRACT

Epithelial Ovarian Cancer (EOC) is associated with dismal survival rates due to the fact that patients are frequently diagnosed at an advanced stage and eventually become resistant to traditional chemotherapeutics. Hence, there is a crucial need for new and innovative therapies. Septin-2, a member of the septin family of GTP binding proteins, has been characterized in EOC for the first time and represents a potential future target. Septin-2 was found to be overexpressed in serous and clear cell human patient tissue compared to benign disease. Stable septin-2 knockdown clones developed in an ovarian cancer cell line exhibited a significant decrease in proliferation rates. Comparative label-free proteomic analysis of septin-2 knockdown cells revealed differential protein expression of pathways associated with the TCA cycle, acetyl CoA, proteasome and spliceosome. Further validation of target proteins indicated that septin-2 plays a predominant role in post-transcriptional and translational modifications as well as cellular metabolism, and suggested the potential novel role of septin-2 in promoting EOC tumorigenesis through these mechanisms.

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Research Papers:

Septin-2 is overexpressed in epithelial ovarian cancer and mediates proliferation via regulation of cellular metabolic proteins

Abstract