The role of pluripotency factors to drive stemness in gastrointestinal cancer

• Published in: Stem cell research 2016-03, Vol.16 (2), p.349-357
• Main Authors: Müller, Martin, Hermann, Patrick C., Liebau, Stefan, Weidgang, Clair, Seufferlein, Thomas, Kleger, Alexander, Perkhofer, Lukas
• Format: Article
• Language: English
• Subjects: Carcinogenesis; Cellular Reprogramming; Epithelial-Mesenchymal Transition; Gastrointestinal Neoplasms - metabolism; Gastrointestinal Neoplasms - pathology; Humans; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - metabolism; Octamer Transcription Factor-3 - genetics; Octamer Transcription Factor-3 - metabolism; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; SOXB1 Transcription Factors - genetics; SOXB1 Transcription Factors - metabolism; Stem Cells - cytology; Stem Cells - metabolism
• ISSN: 1873-5061; 1876-7753
• DOI: 10.1016/j.scr.2016.02.005

A better molecular understanding of gastrointestinal cancers arising either from the stomach, the pancreas, the intestine, or the liver has led to the identification of a variety of potential new molecular therapeutic targets. However, in most cases surgery remains the only curative option. The intratumoral cellular heterogeneity of cancer stem cells, bulk tumor cells, and stromal cells further limits straightforward targeting approaches. Accumulating evidence reveals an intimate link between embryonic development, stem cells, and cancer formation. In line, a growing number of oncofetal proteins are found to play common roles within these processes. Cancer stem cells share features with true stem cells by having the capacity to self-renew in a de-differentiated state, to generate heterogeneous types of differentiated progeny, and to give rise to the bulk tumor. Further, various studies identified genes in cancer stem cells, which were previously shown to regulate the pluripotency circuitry, particularly the so-called “Yamanaka-Factors” (OCT4, KLF4, SOX2, and c-MYC). However, the true stemness potential of cancer stem cells and the role and expression pattern of such pluripotency genes in various tumor cell types remain to be explored. Here, we summarize recent findings and discuss the potential mechanisms involved, and link them to clinical significance with a particular focus on gastrointestinal cancers. There is an link between embryonic development, stem cells, and cancer formation•Cancer stem cells share features with true stem cells•Cancer stem cells contain genes that are known to regulate the pluripotency circuitry