The Expanding Network of p53 Signaling: Reaching to the Unknown of Cancer

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Background

The tumor suppressor p53 is regarded as guardian of the genome by preventing malignant transformation and tumorigenesis. In response to various stress signals, such as DNA damage, nucleolar stress, hypoxia, and nutrient depletion, p53 is activated to induce cell cycle arrest, DNA repair, senescence, apoptosis, autophagy, ferroptosis, and etc. Because of p53's extreme cytotoxic effect, cancer cells utilize multiple strategies to inactivate p53 in favor of their own survival and propagation. The E3 ubiquitin ligase MDM2, encoded by a p53 target gene that is often amplified in cancer, is the master negative regulator of p53. In addition, a myriad of oncoproteins and non-coding RNAs have been found to inhibit p53 activity. In around 50% of human cancers, the TP53 gene is mutated or deleted, which not only abrogates the tumor suppressive function of wild-type p53, but also endows mutant proteins with "dominant-negative" activity or oncogenic "gain of function". Particularly, several hotspot mutants are able to promote cancer formation, progression and resistance to therapies. More than 40 years study leads to a hundred thousand publications in the field of p53, which constitutes a treasure house of knowledge about etiology and treatment of cancer, and will certainly contribute to eventual defeat of the disease.

Accumulating evidence has been unveiling novel roles of both p53 and mutant p53 in remodeling cancer metabolism, fostering tumor microenvironment, and orchestrating therapy response. This Research Topic aims at the investigations of new functions and regulations of p53/mutant p53 in cancer. In addition, although p53/mutant p53 have been raised to the core position of the signaling network of cancer, the translation of our knowledge into clinical use remains limited. This collection of studies also focuses on highlighting potential clinical relevance of p53/mutant p53 in the light of their expanding tentacles reaching to most aspects of cancer.

Original research articles and review articles on all aspects of functions and molecular basis of p53 and mutant p53 are welcome. Areas of interest include, but are not limited to:
1) p53 and metabolism
2) p53 and immune response
3) p53 and tumor microenvironment
4) p53 and cancer therapies
5) novel regulators of p53

Keywords: P53, Non-coding RNA, Metabolism, Cancer Therapy, Tumor Microenvironment

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