Function and clinical relevance of RHAMM isoforms in pancreatic tumor progression Research Letter
| Authors: | Choi, S.; Wang, D.; Chen, X.; Tang, L. H.; Verma, A.; Chen, Z.; Kim, B. J.; Selesner, L.; Robzyk, K.; Zhang, G.; Pang, S.; Han, T.; Chan, C. S.; Fahey, T. J. 3rd; Elemento, O.; Du, Y. C. N. |
| Title: | Function and clinical relevance of RHAMM isoforms in pancreatic tumor progression |
| Abstract: | The receptor for hyaluronic acid-mediated motility (RHAMM) is upregulated in various cancers. We previously screened genes upregulated in human hepatocellular carcinomas for their metastatic function in a mouse model of pancreatic neuroendocrine tumor (PNET) and identified that human RHAMM B promoted liver metastasis. It was unknown whether RHAMM B is upregulated in pancreatic cancer or contributes to its progression. In this study, we found that RHAMM protein was frequently upregulated in human PNETs. We investigated alternative splicing isoforms, RHAMM A and RHAMM B , by RNA-Seq analysis of primary PNETs and liver metastases. RHAMM B , but not RHAMM A , was significantly upregulated in liver metastases. RHAMM B was crucial for in vivo metastatic capacity of mouse and human PNETs. RHAMM A , carrying an extra 15-amino acid-stretch, did not promote metastasis in spontaneous and experimental metastasis mouse models. Moreover, RHAMM B was substantially higher than RHAMM A in pancreatic ductal adenocarcinoma (PDAC). RHAMM B , but not RHAMM A , correlated with both higher EGFR expression and poorer survival of PDAC patients. Knockdown of EGFR abolished RHAMM B -driven PNET metastasis. Altogether, our findings suggest a clinically relevant function of RHAMM B , but not RHAMM A , in promoting PNET metastasis in part through EGFR signaling. RHAMM B can thus serve as a prognostic factor for pancreatic cancer. © 2019 The Author(s). |
| Keywords: | cancer survival; controlled study; unclassified drug; nonhuman; protein function; mouse; animal tissue; metastasis; gene expression; epidermal growth factor receptor; animal experiment; animal model; in vivo study; liver metastasis; pancreas tumor; isoforms; alternative rna splicing; pancreas adenocarcinoma; upregulation; receptor; pancreatic cancer; egfr gene; tumor growth; rna sequence; pancreas islet cell tumor; rhamm; article; pdac; pnets; receptor for hyaluronic acid mediated motility isoform a; receptor for hyaluronic acid mediated motility isoform b |
| Journal Title: | Molecular Cancer |
| Volume: | 18 |
| ISSN: | 1476-4598 |
| Publisher: | Biomed Central Ltd |
| Date Published: | 2019-05-09 |
| Start Page: | 92 |
| Language: | English |
| DOI: | 10.1186/s12943-019-1018-y |
| PUBMED: | 31072393 |
| PROVIDER: | scopus |
| PMCID: | PMC6506944 |
| DOI/URL: | |
| Notes: | Source: Scopus |
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