Abstract
The tumor suppressor p53 is considered the “guardian of the genome” that can protect cells against cancer by inducing cell cycle arrest followed by cell death. However, STAT3 is constitutively activated in several human cancers and plays crucial roles in promoting cancer cell proliferation and survival. Hence, STAT3 and p53 have opposing roles in cellular pathway regulation, as activation of STAT3 upregulates the survival pathway, whereas p53 triggers the apoptotic pathway. Constitutive activation of STAT3 and gain or loss of p53 function due to mutations are the most frequent events in numerous cancer types. Several studies have reported the association of STAT3 and/or p53 mutations with drug resistance in cancer treatment. This review discusses the relationship between STAT3 and p53 status in cancer, the molecular mechanism underlying the negative regulation of p53 by STAT3, and vice versa. Moreover, it underlines prospective therapies targeting both STAT3 and p53 to enhance chemotherapeutic outcomes.
Highlights
Cancer is one of the leading causes of death worldwide, which was responsible for approximately9.6 million cancer deaths in 2018 [1]
Despite the multifaceted function of support transcription 3 (STAT3) in cancer, growing evidence has revealed that constitutive activation of STAT3 contributes to cancer cell proliferation and that aberrant STAT3 activation is associated with tumor malignancy [14,15,16]
STAT3 acts as a transcription factor that activates several downstream target genes that are involved in multiple steps of metastasis, including invasion, cell survival, self-renewal, angiogenesis, and tumor-cell immune evasion [53]
Summary
Cancer is one of the leading causes of death worldwide, which was responsible for approximately. Signal transduction and activator of transcription (STAT) 3 is a member of the STAT family, comprising seven transcription factors (STAT 1, 2, 3, 4, 5a, 5b, 6) [4] It was discovered by two independent groups [5,6] and has been of particular interest due to its role in the regulation of cellular signaling, especially in cancers. Despite the multifaceted function of STAT3 in cancer, growing evidence has revealed that constitutive activation of STAT3 contributes to cancer cell proliferation and that aberrant STAT3 activation is associated with tumor malignancy [14,15,16]. Tumor cell proliferation and survival involve downregulation of wtp expression as well as increase in STAT3 activity. We have summarized the status of STAT3 and p53 in different cancer cell types and highlighted the potential therapies that target both factors to improve the efficacy of cancer prevention
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