Open AccessCell Cycle Dysregulation in Oral Cancer
Author(s) -
Randy Todd,
Phil W. Hinds,
Karl Münger,
Anil K. Rustgi,
Oliver G. Opitz,
Yasir Suliman,
David T. Wong
Publication year - 2002
Publication title -
critical reviews in oral biology and medicine
Language(s) - English
Resource type - Journals
eISSN - 1544-1113
pISSN - 1045-4411
DOI - 10.1177/154411130201300106
Subject(s) - cell cycle , cyclin dependent kinase , carcinogenesis , microbiology and biotechnology , retinoblastoma protein , cell cycle checkpoint , biology , senescence , cyclin , signal transduction , cell cycle protein , cdk inhibitor , cyclin d1 , cell growth , cyclin dependent kinase 1 , cancer research , cell , cancer , biochemistry , genetics
The dysregulation of the molecular events governing cell cycle control is emerging as a central theme of oral carcinogenesis. Regulatory pathways responding to extracellular signaling or intracellular stress and DNA damage converge on the cell cycle apparatus. Abrogation of mitogenic and anti-mitogenic response regulatory proteins, such as the retinoblastoma tumor suppressor protein (pRB), cyclin D1, cyclin-dependent kinase (CDK) 6, and CDK inhibitors (p21 WAF1/CIP1 , p27 KIP1 , and p16 INK4a ), occur frequently in human oral cancers. Cellular responses to metabolic stress or genomic damage through p53 and related pathways that block cell cycle progression are also altered during oral carcinogenesis. In addition, new pathways and cell cycle regulatory proteins, such as p12 DOC-1 , are being discovered. The multistep process of oral carcinogenesis likely involves functional alteration of cell cycle regulatory members combined with escape from cellular senescence and apoptotic signaling pathways. Detailing the molecular alterations and understanding the functional consequences of the dysregulation of the cell cycle apparatus in the malignant oral keratinocyte will uncover novel diagnostic and therapeutic approaches.