Published online Jun 26, 2020. doi: 10.4252/wjsc.v12.i6.481
Peer-review started: January 15, 2020
First decision: March 16, 2020
Revised: April 7, 2020
Accepted: May 5, 2020
Article in press: May 5, 2020
Published online: June 26, 2020
Cancer cells possess metabolic properties that are different from those of benign cells. p21, encoded by CDKN1A gene, also named p21Cip1/WAF1, was first identified as a cyclin-dependent kinase regulator that suppresses cell cycle G1/S phase and retinoblastoma protein phosphorylation. CDKN1A (p21) acts as the downstream target gene of TP53 (p53), and its expression is induced by wild-type p53 and it is not associated with mutant p53. p21 has been characterized as a vital regulator that involves multiple cell functions, including G1/S cell cycle progression, cell growth, DNA damage, and cell stemness. In 1994, p21 was found as a tumor suppressor in brain, lung and colon cancer by targeting p53 and was associated with tumorigenesis and metastasis. Notably, p21 plays a significant role in tumor development through p53-dependent and p53-independent pathways. In addition, expression of p21 is closely related to the resting state or terminal differentiation of cells. p21 is also associated with cancer stem cells and acts as a biomarker for such cells. In cancer therapy, given the importance of p21 in regulating the G1/S and G2 check points, it is not surprising that p21 is implicated in response to many cancer treatments and p21 promotes the effect of oncolytic virotherapy.
Core tip: p21, as a cyclin-dependent kinase regulator, suppresses cell cycle G1/S phase and retinoblastoma protein phosphorylation. As the downstream target gene of TP53, p21 expression is induced by wild-type p53. p21 was found as a tumor suppressor in several cancers by targeting p53 and was associated with tumorigenesis and metastasis. Notably, p21 is also associated with cancer stem cells. Moreover, p21 is closely related to cancer therapy, and it can promote antitumor effect of oncolytic virotherapy. These findings implicated multifaceted roles of p21 in cancer treatment.