The Roles and Molecular Mechanisms of Nestin Expression in Cancer with a Focus on Pancreatic Cancer
Yoko Matsuda, Hisashi Yoshimura, Zenya Naito and Toshiyuki Ishiwata*
Departments of Pathology and Integrative Oncological Pathology, Nippon Medical School, Tokyo, Japan
- *Corresponding Author:
- Toshiyuki Ishiwata
Director of Molecular Pathology Group
Departments of Pathology and Integrative Oncological Pathology
Nippon Medical School, 1-1-5 Sendagi
Bunkyo-ku, Tokyo 113-8602, Japan
Tel: +81-3-822-2131 ext. (5232)
E-mail: [email protected]
Received Date: March 06, 2013; Accepted Date: June 04, 2013; Published Date: June 15, 2013
Citation: Matsuda Y, Yoshimura H, Naito Z, Ishiwata T (2013) The Roles and Molecular Mechanisms of Nestin Expression in Cancer with a Focus on Pancreatic Cancer. J Carcinogene Mutagene S9:002. doi: 10.4172/2157-2518.S9-002
Copyright: © 2013 Matsuda Y, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Nestin is a class VI intermediate filament protein that is expressed in a variety of stem and progenitor cells, including primitive neuroepithelial cells and pancreatic exocrine progenitor cells. Nestin expression is closely associated with rapidly proliferating progenitor cells during development and repair processes, and higher nestin expression levels correlate with poor prognosis in some cancers. Nestin regulates many molecules during cell processes in both normal and neoplastic tissues, and its transcription is regulated by enhancer regions in the second intron of the nestin gene that bind to SOX, Class III POU, and N-Myc. Nestin forms heterodimers with other intermediate filaments, with the class III intermediate filament protein vimentin being its main partner. Nestin/ vimentin copolymers provide an anchor for glucocorticoid receptors, regulate insulin-degrading enzyme, and promote the phosphorylation-dependent disassembly of vimentin during mitosis. Nestin regulates cell proliferation, the cell cycle, cell survival, and apoptosis by regulating cyclin-dependent kinase-5 (Cdk5), phosphoinositide 3-kinase, and AKT. We reported previously that nestin regulates cell motility, invasiveness, and cell morphology in a pancreatic cancer cell line via regulation of F-actin and E-cadherin. This review focuses on the roles of nestin in cancer stem cells and in tumor-initiating cells in the pancreas. In the pancreas, nestin plays important roles in the proliferation, differentiation, and survival of both progenitor cells and cancer cells.