Abstract
p53 has functional roles in tumor suppression as a guardian of the genome, surveillant of oncogenic cell transformation, and as recently demonstrated, a regulator of intracellular metabolism. Accumulating evidence has shown that the tumor microenvironment, accompanied by inflammation and tissue remodeling, is important for cancer proliferation, metastasis, and maintenance of cancer stem cells (CSCs) that self-renew and generate the diverse cells comprising the tumor. Furthermore, p53 has been demonstrated to inhibit inflammatory responses, and functional loss of p53 causes excessive inflammatory reactions. Moreover, the generation and maintenance of CSCs are supported by the inflammatory tumor microenvironment. Considering that the functions of p53 inhibit reprogramming of somatic cells to stem cells, p53 may have a major role in the inflammatory microenvironment as a tumor suppressor. Here, we review our current understanding of the mechanisms underlying the roles of p53 in regulation of the inflammatory microenvironment, tumor microenvironment, and tumor suppression.
Highlights
Increasing evidence has indicated that oncogenesis is a multistep process that reflects genetic alterations driving the progressive transformation of normal cells into highly malignant derivatives [1,2]
Such genetic alterations produce oncogenes with a dominant gain of function and tumor suppressor genes with a recessive loss of function. p53 is the most frequently mutated gene in human cancer cells [3]. It functions as a transcriptional activator and exerts its biological activity by inducing the expression of its target genes [4]. p53 is regulated by the ubiquitin E3 ligase Mdm2 that targets p53 for proteasomal degradation
We have found that p53 directly suppresses transcriptional activity of the nuclear factor-κB (NF-κB) subunit p65 through inhibition of p65 binding and p65 activation by IκB kinase (IKK) β [66]
Summary
Increasing evidence has indicated that oncogenesis is a multistep process that reflects genetic alterations driving the progressive transformation of normal cells into highly malignant derivatives [1,2]. In response to various cellular stresses, such as DNA damage, hypoxia, and nutrient deprivation, p53 induces the expression of genes regulating the cell cycle, apoptosis, and DNA repair [4,5,6] Through these functions, p53 prevents passing on altered genetic information evoked by DNA damage and has been termed the “guardian of the genome” [7,8]. The p53-mediated tumor surveillance system, which responds to oncogenic signals evoked by oncogene activation, triggers apoptosis or cell cycle arrest, resulting in the elimination of oncogene-activated cells by cell death or induction of senescence [5,7,9] Inactivation of this system by the loss of p53 functions is a critical step in cancer development. This review will focus on the roles of p53 in regulation of the inflammatory tumor microenvironment, including the generation and maintenance of cancer stem cells (CSCs) and tumor suppression
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
