Genomic models of metastatic cancer: functional analysis of death-from-cancer signature genes reveals aneuploid, anoikis-resistant, metastasis-enabling phenotype with altered cell cycle control and activated Polycomb Group (PcG) protein chromatin silencing pathway.
A recent discovery of death-from-cancer signature genes identifies potential markers predicting the high likelihood of treatment failure in cancer patients. This knowledge provides the opportunity to analyze in functional terms the therapy-resistant and metastasis-enabling phenotypes of cancer cells. Here we summarize the current data regarding the biological functions of genes comprising a death-from-cancer signature. This analysis predicts that cancer cells manifesting a stem cell-like expression profile of a death-from-cancer signature would exhibit the following features: a concomitantly increased expression of certain members of inhibitor of apoptosis protein (IAP) family (Survivin and XIAP); activation of mitotic spindle check point proteins (BUB1, BUB3, KNTC2, Mad2, PLK1, PLK4, STK6/Aurora A); and elevated levels of certain cell cycle control/marker proteins (CCNB1, CCNB2, CCND1, CCNA2, CDC2, CDC25, Ki67, USP22). Consequently, these cancer cells would acquire metastasis-enabling anoikis-resistance aneuploid phenotype with aberrant cell cycle control. A functionally complementary role of multiple cooperating oncogenic pathways and the essential role of Polycomb Group (PcG) protein chromatin silencing pathway in emergence of the stem cell cancer phenotype is highlighted.
Glinsky
Gennadi V
GV
Functional Genomics Laboratory, Ordway Cancer Center, Ordway Research Institute, Inc., Center for Medical Sciences, Division of Urology, Albany Medical College, New York 12208 USA. GGlinsky@ordwayresearch.org
D000782:Aneuploidy; D023102:Anoikis; D002453:Cell Cycle; D002843:Chromatin; D020868:Gene Silencing; D006801:Humans; D008957:Models, Genetic; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D009369:Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D017211:Treatment Failure
D002843:Chromatin; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins