p53 in cell invasion, podosomes, and invadopodia

Abstract

Cell invasion of the extracellular matrix is prerequisite to cross tissue migration of tumor cells in cancer metastasis, and vascular smooth muscle cells in atherosclerosis. The tumor suppressor p53, better known for its roles in the regulation of cell cycle and apoptosis, has ignited much interest in its function as a suppressor of cell migration and invasion. How p53 and its gain-of-function mutants regulate cell invasion remains a puzzle and a challenge for future studies. In recent years, podosomes and invadopodia have also gained center stage status as veritable apparatus specialized in cell invasion. It is not clear, however, whether p53 regulates cell invasion through podosomes and invadopodia. In this review, evidence supporting a negative role of p53 in podosomes formation in vascular smooth muscle cells will be surveyed, and signaling nodes that may mediate this regulation in other cell types will be explored.

PCDH10, a novel p53 transcriptional target in regulating cell migration

“…17 It has been observed for long time that the deletion of p53 allows fibroblast to migrate faster in wound healing assays, potentially due to the altered cell morphology and polarity. 14,21 This observation is not only limited to fibroblast, but also expanded to multiple cancer epithelial cell lines. 14,21 However, the underlying molecular mechanism of this regulation is, at least partially, kept unknown and requires delineated studies.…”

“…14,21 This observation is not only limited to fibroblast, but also expanded to multiple cancer epithelial cell lines. 14,21 However, the underlying molecular mechanism of this regulation is, at least partially, kept unknown and requires delineated studies. It was discovered that the loss of p53 activates Rho signaling pathway, a well-established pathway to influence the way in which tumor cells migrate, to promote cell migration.…”

“…17,26 Further, tumor derived mutant p53 enhances integrin and epidermal growth factor receptor (EGFR) trafficking therefore promotes cell migration and invasion. 14,16 Numerous proteins have been linked to the p53's ability in controlling cell migration and metastasis, such as Rho GTPases (Cdc42,RhoE,Caldesmon), EMC(extra cellular matrix)protein MMP-2, growth factor EGFR, and PTEN etc. ; however, most of these mediators of p53 in regulating cell migration and metastasis are repressed targets of p53, secondary transcriptional targets of p53, or regulated molecules by p53 in a transcriptional-independent manner.…”

A DDX31/Mutant–p53/EGFR Axis Promotes Multistep Progression of Muscle-Invasive Bladder Cancer

“…Mutant p53 proteins (mutp53) lose wild-type p53 (wtp53) transcriptional activity and gain novel oncogenic functions that are independent of wtp53 (7). Accumulating evidence has recently revealed that mutp53 can promote invasion and motility through its activation of transforming growth factor  (TGF-), epidermal growth factor receptor (EGFR) and MET (8).…”

Invadosomes in real life

“…10 The number of cell types described to be able to form invadosomes is constantly increasing. Depending on the cell-specific functions and the extracellular context studied, invadosomes' molecular composition and the associated signaling pathways can differ.…”