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.