Understanding p53: new insights into tumor suppression

Abstract

p53 (aka TP53) is a powerful tumor suppressor, and oncogenic transformation is induced when the ability of p53 to suppress tumorigenesis is compromised. p53 not only prevents tumorigenesis, but also tumor progression, that is, local invasion and distant metastasis. Recently, we showed that cytoplasmic p53 prevents RAS-driven invasion via alteration of actin cytoskeleton remodeling. This follows modulation of mitochondrial integrity. The transcriptional activity of p53 has been restored using small molecules; however, their success as cancer therapies is largely dependent on the status of downstream targets of p53. It is therefore important to elucidate the role of these downstream targets in p53 regulated tumor progression. With the recently described mechanism of tumor suppression highlighting a role of p53’s downstream targets in the regulation of actin cytoskeleton dynamics and lamellipodia formation, we suggest that potential therapeutic targets may be revealed within this mechanism that can be exploited in anticancer therapy.

Keywords::

• actin
• apoptosis
• invasion
• p53
• RAS

Financial & competing interests disclosure

This work was supported by the National Research Foundation, Singapore and the Ministry of Education, Singapore through the Mechanobiology Institute in the National University of Singapore. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.