title: Cancer stem cells and epithelial-mesenchymal transition: Novel therapeutic targets for cancer.
abstract: Despite the development of various therapeutic approaches, recurrence and metastasis remain major problems for patients with advanced cancer. Recent studies have shown that cancer stem cells (CSCs) play an important role in cancer aggressiveness. In cancer tissues, a small number of CSCs are able to self-renew and differentiate into heterogeneous cancer cells. CSCs usually remain in the resting phase of the cell cycle and possess efficient drug efflux pathways. Thus, they are resistant to chemoradiotherapy and surviving CSCs contribute to recurrence. During cancer metastasis, CSCs undergo epithelial-mesenchymal transition (EMT), thereby acquiring mesenchymal features, migrating to adjacent stromal tissues, and invading blood or lymph vessels. Recent studies showed that EMT-inducible factors also enhance or induce CSC-like features in cancer cells. These findings suggest that EMT is closely correlated with cancer recurrence and metastasis. Inhibition of nestin, a CSC marker, reduces the aggressiveness of several types of cancer. Suppression of the mesenchymal variant of fibroblast growth factor (FGFR)-2, FGFR-2 IIIc, and regulation of the EMT using epithelial splicing regulatory protein 1 (ESRP1) are effective in the treatment of immunodeficient mice with pancreatic cancer. The roles of CSCs and EMT in cancer and possible therapies are discussed in this review.
authors: Division of Aging and Carcinogenesis, Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. tishiwat@tmig.or.jp.
authors: Toshiyuki
authors: T
authors: Ishiwata
mesh_terms: D000818:Animals; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D006801:Humans; D014411:Neoplastic Stem Cells / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000503:physiopathology* / Q000628:therapy*; D016601:RNA-Binding Proteins / Q000378:metabolism
chemical_list: C539364:ESRP1 protein, human; D016601:RNA-Binding Proteins
keywords: cancer stem cell; epithelial splicing regulatory protein 1/ESRP1; epithelial-mesenchymal transition; fibroblast growth factor receptor-2/FGFR-2; nestin