Format

Send to

Choose Destination
Cancer Metastasis Rev. 2010 Dec;29(4):613-39. doi: 10.1007/s10555-010-9257-9.

The guardians of the genome (p53, TA-p73, and TA-p63) are regulators of tumor suppressor miRNAs network.

Author information

1
Genome Discovery, 49, Nattar Main Street, Puducherry 605 004, India. lakshmanan.boominathan@gmail.com

Abstract

The tumor suppressor p53 homologues, TA-p73, and p63 have been shown to function as tumor suppressors. However, how they function as tumor suppressors remains elusive. Here, I propose a number of tumor suppressor pathways that illustrate how the TA-p73 and p63 could function as negative regulators of invasion, metastasis, and cancer stem cells (CSCs) proliferation. Furthermore, I provide molecular insights into how TA-p73 and p63 could function as tumor suppressors. Remarkably, the guardians--p53, p73, and p63--of the genome are in control of most of the known tumor suppressor miRNAs, tumor suppressor genes, and metastasis suppressors by suppressing c-myc through miR-145/let-7/miR-34/TRIM32/PTEN/FBXW7. In particular, p53 and TA-p73/p63 appear to upregulate the expression of (1) tumor suppressor miRNAs, such as let-7, miR-34, miR-15/16a, miR-145, miR-29, miR-26, miR-30, and miR-146a; (2) tumor suppressor genes, such as PTEN, RBs, CDKN1a/b/c, and CDKN2a/b/c/d; (3) metastasis suppressors, such as Raf kinase inhibitory protein, CycG2, and DEC2, and thereby they enlarge their tumor suppressor network to inhibit tumorigenesis, invasion, angiogenesis, migration, metastasis, and CSCs proliferation.

PMID:
20922462
DOI:
10.1007/s10555-010-9257-9
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center