MUC13 overexpression in renal cell carcinoma plays a central role in tumor progression and drug resistance

Sheng, Yonghua, Ng, Choa Ping, Lourie, Rohan, Shah, Esha T., He, Yaowu, Wong, Kuan Yua, Seim, Inge, Oancea, Iulia, Morais, Christudas, Jeffery, Penny L., Hooper, John, Gobe, Glenda C. and Mcguckin, Michael A. (2017) MUC13 overexpression in renal cell carcinoma plays a central role in tumor progression and drug resistance. International Journal of Cancer, . doi:10.1002/ijc.30651


Author Sheng, Yonghua
Ng, Choa Ping
Lourie, Rohan
Shah, Esha T.
He, Yaowu
Wong, Kuan Yua
Seim, Inge
Oancea, Iulia
Morais, Christudas
Jeffery, Penny L.
Hooper, John
Gobe, Glenda C.
Mcguckin, Michael A.
Title MUC13 overexpression in renal cell carcinoma plays a central role in tumor progression and drug resistance
Journal name International Journal of Cancer   Check publisher's open access policy
ISSN 1097-0215
0020-7136
Publication date 2017-02-28
Sub-type Article (original research)
DOI 10.1002/ijc.30651
Open Access Status Not yet assessed
Total pages 13
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Collection year 2018
Language eng
Formatted abstract
Metastatic renal cell carcinoma is a largely incurable disease, and existing treatments targeting angiogenesis and tyrosine kinase receptors are only partially effective. Here we reveal that MUC13, a cell surface mucin glycoprotein, is aberrantly expressed by most renal cell carcinomas, with increasing expression positively correlating with tumor grade. Importantly, we demonstrated that high MUC13 expression was a statistically significant independent predictor of poor survival in two independent cohorts, particularly in stage 1 cancers. In cultured renal cell carcinoma cells MUC13 promoted proliferation and induced the cell cycle regulator, cyclin D1, and inhibited apoptosis by inducing the anti-apoptotic proteins, BCL-xL and survivin. Silencing of MUC13 expression inhibited migration and invasion, and sensitized renal cancer cells to killing by the multi-kinase inhibitors used clinically, sorafenib and sunitinib, and reversed acquired resistance to these drugs. Furthermore, we demonstrated that MUC13 promotion of renal cancer cell growth and survival is mediated by activation of nuclear factor κB, a transcription factor known to regulate the expression of genes that play key roles in the development and progression of cancer. These results show that MUC13 has potential as a prognostic marker for aggressive early stage renal cell cancer and is a plausible target to sensitize these tumors to therapy.
Keyword Apoptosis sorafenib
MUC13
NFκB
Prognostic marker
Proliferation
Renal cell carcinoma
Sunitinib
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
HERDC Pre-Audit
UQ Diamantina Institute Publications
 
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