Cell Cycle and Cancer

Abstract

Cancer is frequently considered to be a disease of the cell cycle. As such, it is not surprising that the deregulation of the cell cycle is one of the most frequent alterations during tumor development. Cell cycle progression is a highlyordered and tightly-regulated process that involves multiple checkpoints that assess extracellular growth signals, cell size, and DNA integrity. Cyclin-dependent kinases (CDKs) and their cyclin partners are positive regulators or accelerators that induce cell cycle progression; whereas, cyclindependent kinase inhibitors (CKIs) that act as brakes to stop cell cycle progression in response to regulatory signals are important negative regulators. Cancer originates from the abnormal expression or activation of positive regulators and functional suppression of negative regulators. Therefore, understanding the molecular mechanisms of the deregulation of cell cycle progression in cancer can provide important insights into how normal cells become tumorigenic, as well as how new cancer treatment strategies can be designed.

Silibinin Inhibits Proliferation, Induces Apoptosis and Causes Cell Cycle Arrest in Human Gastric Cancer MGC803 Cells Via STAT3 Pathway Inhibition

“…Cancer is frequently considered to be a disease of the cell cycle (Ambrosini et al, 1997). Several studies have suggested that inhibition of cell cycle regulation in cancer cells could be a potential target for the management of cancer (Park et al, 2003;Williams et al, 2012). Collectively, recent studies show that silibinin caused cell cycle arrest in different phases in various cancer cells.…”

Cell survival, cell death and cell cycle pathways are interconnected: Implications for cancer therapy

“…After passing these checkpoints cells are irreversibly committed to the next phase (Park and Lee, 2003). DNA damage and/or malfunction of other critical organelles or structures (e.g.…”

“…CDKs, the key regulator proteins, which in connection with their positive regulators, cyclins, allow the transition from one cell cycle phase to another, are also tightly regulated by inhibitory phosphorylation and by inhibitory molecules. The inhibitory phosphorylation is mediated by the kinase Wee1 and MYT1 (Park and Lee, 2003). CDKs can also be inhibited by two classes of CDK inhibitors, the INK4 group such as p16 Ink4a or p15 Ink4b and the CIP/KIP class such as p21 waf1 or p27 kip1 (Park and Lee, 2003;Grant and Roberts, 2003;Schwartz and Shah, 2005).…”

“…The key regulator proteins which allow the transition from one cell cycle phase to another are called cyclin-dependent kinases (CDKs), a family of serine/threonine protein kinases which are activated at specific points during cell cycle (Collins and Garrett, 2005;Vermeulen et al, 2003). Positive regulation of CDK activity occurs through association with a second subunit, the cyclin and by phosphorylation of the T-loop threonine by a CDKactivating kinase (Park and Lee, 2003). Cyclins are produced at each of these phases and form a complex with their CDK partners.…”

Genome-wide identification of cancer-related polyadenylated and non-polyadenylated RNAs in human breast and lung cell lines

“…The transcripts affected are involved in cell cycle regulation; therefore, it is conceivable that cell proliferation would be further influenced. Ultimately, tumorigenesis is triggered because of inappropriate cell proliferation [33]. Similarly, inappropriate apoptosis may cause tumorigenesis because apoptosis can serve as a natural barrier to cancer development [19].…”