DCLK1 is a broadly dysregulated target against epithelial-mesenchymal transition, focal adhesion, and stemness in clear cell renal carcinoma

摘要: // Nathaniel Weygant 1 , Dongfeng Qu 1,2,3 Randal May 1,2 Ryan M. Tierney William L. Berry 4 Lichao Zhao 5 Shweta Agarwal Parthasarathy Chandrakesan Harisha R. Chinthalapally Nicholas T. Murphy James D. Li Sripathi Sureban Michael J. Schlosser 6 Tomasek and Courtney W. Houchen 1,2,3,6 Department of Medicine, University Oklahoma Health Sciences Center, Oklahoma, OK 2 Veterans Affairs Medical 3 Peggy Charles Stephenson Cancer Cell Biology, Pathology, COARE Biotechnology, Correspondence: Houchen, email: Keywords : DCLK1, Renal Carcinoma, Tumor Stem Cell, Focal Adhesion, EMT Received October 31, 2014 Accepted December 10, Published 11, Abstract clear cell carcinoma (RCC) is the most common type kidney cancer 8 th overall in US. RCC survival rates drop precipitously with regional distant spread recent studies have demonstrated that presents an epithelial-mesenchymal transition (EMT) phenotype linked to increased recurrence decreased survival. a key characteristic tumor stem cells (TSCs) along chemo-resistance radio-resistance, which are also phenotypic RCC. Targeting these factors increasing patients. Doublecortin-like kinase (DCLK1) marks TSCs pancreatic colorectal regulates stemness. Analysis Genome Atlas’ dataset revealed DCLK1 overexpressed dysregulated on mRNA epigenetic level more than 93% tumors relative adjacent normal tissue. Immunohistochemistry using α-DCLK1 antibody confirmed overexpression major increase immunoreactivity stage II-III compared I tumors. Small-interfering RNA (siRNA) mediated knockdown resulted expression pluripotency significantly reduced invasion, migration, focal adhesion, drug-resistance, clonogenic capacity. These findings suggest novel, factor progression may be targeted suppress EMT, metastasis, stemness early-stage advanced patient Moreover, possibility mark population stem-like should further investigated light findings.