title: Rad6 upregulation promotes stem cell-like characteristics and platinum resistance in ovarian cancer.
abstract: Ovarian cancer is the fifth most deadly cancer in women in the United States and despite advances in surgical and chemotherapeutic treatments survival rates have not significantly improved in decades. The poor prognosis for ovarian cancer patients is largely due to the extremely high (80%) recurrence rate of ovarian cancer and because the recurrent tumors are often resistant to the widely utilized platinum-based chemotherapeutic drugs. In this study, expression of Rad6, an E2 ubiquitin-conjugating enzyme, was found to strongly correlate with ovarian cancer progression. Furthermore, in ovarian cancer cells Rad6 was found to stabilize β-catenin promoting stem cell-related characteristics, including expression of stem cell markers and anchorage-independent growth. Cancer stem cells can promote chemoresistance, tumor recurrence and metastasis, all of which are limiting factors in treating ovarian cancer. Thus it is significant that Rad6 overexpression led to increased resistance to the chemotherapeutic drug carboplatin and correlated with tumor cell invasion. These findings show the importance of Rad6 in ovarian cancer and emphasize the need for further studies of Rad6 as a potential target for the treatment of ovarian cancer.
authors.affiliation: Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Avenue, Mobile, AL 36604, USA.
authors.forename: Ranganatha R
authors.initials: RR
authors.lastname: Somasagara
authors.affiliation: Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Avenue, Mobile, AL 36604, USA.
authors.forename: Kaushlendra
authors.initials: K
authors.lastname: Tripathi
authors.affiliation: Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Avenue, Mobile, AL 36604, USA.
authors.forename: Sebastian M
authors.initials: SM
authors.lastname: Spencer
authors.affiliation: Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Avenue, Mobile, AL 36604, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Clark
authors.affiliation: Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Avenue, Mobile, AL 36604, USA.
authors.forename: Reagan
authors.initials: R
authors.lastname: Barnett
authors.affiliation: Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Avenue, Mobile, AL 36604, USA.
authors.forename: Lavanya
authors.initials: L
authors.lastname: Bachaboina
authors.affiliation: Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Avenue, Mobile, AL 36604, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Scalici
authors.affiliation: Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Avenue, Mobile, AL 36604, USA.
authors.forename: Rodney P
authors.initials: RP
authors.lastname: Rocconi
authors.affiliation: Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Avenue, Mobile, AL 36604, USA.
authors.forename: Gary A
authors.initials: GA
authors.lastname: Piazza
authors.affiliation: Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Avenue, Mobile, AL 36604, USA. Electronic address: kpalle@health.southalabama.edu.
authors.forename: Komaraiah
authors.initials: K
authors.lastname: Palle
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D017671:Platinum Compounds / Q000008:administration & dosage*; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D017671:Platinum Compounds; D044763:Ubiquitin-Conjugating Enzymes
keywords: Ovarian cancer; Platinum resistance; Rad6; Stem cell