PMID- 26304749 OWN - NLM STAT- MEDLINE DCOM- 20160725 LR - 20181202 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 5 DP - 2015 Aug 25 TI - HCRP-1 regulates cell migration and invasion via EGFR-ERK mediated up-regulation of MMP-2 with prognostic significance in human renal cell carcinoma. PG - 13470 LID - 10.1038/srep13470 [doi] LID - 13470 AB - Previous studies indicated a role of hepatocellular carcinoma-related protein-1(HCRP-1) in human cancers, however, its expression pattern in renal cell carcinoma (RCC) and the molecular mechanism of HCRP-1 on cancer progression have not been characterized. In the present study, HCRP-1 expression was examined in a RCC tissue microarray. The negative expression of HCRP-1 was significantly correlated with tumor grade (P = 0.002), TNM stage (P = 0.001) and pT status (P = 0.003). Furthermore, we showed a strong correlation between negative HCRP-1 expression and worse overall and disease-specific survival (P = 0.0003 and P = 0.0012, respectively). Knockdown of HCRP-1 promoted cell migration and invasion in 786-O and OS-RC-2 cell lines. HCRP-1 depletion increased matrix metalloproteinase (MMP)-2 protein level, with increased extracellular signal-regulatedkinase (ERK) phosphorylation, which could be reversed by ERK siRNA or ERK inhibitor, PD98059. Further analysis showed that HCRP-1 knockdown induced epidermal growth factor receptor (EGFR) phosphorylation. Treatment with EGFR inhibitor or EGFR siRNA blocked HCRP-1-mediated up-regulation of EGFR, ERK phosphorylation and MMP-2 expression. In summary, our results showed that negative HCRP-1 expression is an independent prognostic factor for RCC patients and promotes migration and invasion by EGFR-ERK-mediated up-regulation of MMP-2. HCRP-1 may serve as a therapeutic target for RCC. FAU - Chen, Feifei AU - Chen F AD - Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China. FAU - Deng, Junpeng AU - Deng J AD - Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China. AD - Department of Urology, Suzhou Municipal Hospital, Suzhou, China. FAU - Liu, Xin AU - Liu X AD - Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China. FAU - Li, Wang AU - Li W AD - The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China. FAU - Zheng, Junnian AU - Zheng J AD - Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China. AD - The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150825 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Biomarkers, Tumor) RN - 0 (Endosomal Sorting Complexes Required for Transport) RN - 0 (VPS37A protein, human) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 3.4.24.24 (MMP2 protein, human) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) SB - IM EIN - Sci Rep. 2016;6:19412. PMID: 26815012 MH - Biomarkers, Tumor/metabolism MH - Carcinoma, Renal Cell/*metabolism/*mortality/pathology MH - Cell Line, Tumor MH - Cell Movement MH - China/epidemiology MH - Endosomal Sorting Complexes Required for Transport/*metabolism MH - ErbB Receptors/metabolism MH - Humans MH - Incidence MH - Kidney Neoplasms/*metabolism/*mortality/pathology MH - MAP Kinase Signaling System MH - Matrix Metalloproteinase 2/*metabolism MH - Neoplasm Invasiveness MH - Prognosis MH - Reproducibility of Results MH - Risk Factors MH - Sensitivity and Specificity MH - Signal Transduction MH - Survival Rate MH - Up-Regulation PMC - PMC4548257 EDAT- 2015/08/26 06:00 MHDA- 2016/07/28 06:00 PMCR- 2015/08/25 CRDT- 2015/08/26 06:00 PHST- 2015/01/29 00:00 [received] PHST- 2015/07/28 00:00 [accepted] PHST- 2015/08/26 06:00 [entrez] PHST- 2015/08/26 06:00 [pubmed] PHST- 2016/07/28 06:00 [medline] PHST- 2015/08/25 00:00 [pmc-release] AID - srep13470 [pii] AID - 10.1038/srep13470 [doi] PST - epublish SO - Sci Rep. 2015 Aug 25;5:13470. doi: 10.1038/srep13470.