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P38? and Cancer: The Beginning of the Road.

ABSTRACT: The p38 mitogen-activated protein kinase (MAPK) signaling pathway is implicated in cancer biology and has been widely studied over the past two decades as a potential therapeutic target. Most of the biological and pathological implications of p38MAPK signaling are often associated with p38? (MAPK14). Recently, several members of the p38 family, including p38? and p38?, have been shown to play a crucial role in several pathologies including cancer. However, the specific role of p38? (MAPK11) in cancer is still elusive, and further investigation is needed. Here, we summarize what is currently known about the role of p38? in different types of tumors and its putative implication in cancer therapy. All evidence suggests that p38? might be a key player in cancer development, and could be an important therapeutic target in several pathologies, including cancer.

SUBMITTER: Roche O

PROVIDER: S-EPMC7589630 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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p38β and Cancer: The Beginning of the Road.

Roche Olga O Fernández-Aroca Diego M DM Arconada-Luque Elena E García-Flores Natalia N Mellor Liliana F LF Ruiz-Hidalgo María José MJ Sánchez-Prieto Ricardo R

International journal of molecular sciences 20201012 20

The p38 mitogen-activated protein kinase (MAPK) signaling pathway is implicated in cancer biology and has been widely studied over the past two decades as a potential therapeutic target. Most of the biological and pathological implications of p38MAPK signaling are often associated with p38α (MAPK14). Recently, several members of the p38 family, including p38γ and p38δ, have been shown to play a crucial role in several pathologies including cancer. However, the specific role of p38β (MAPK11) in c ...[more]

PMID: 33053909

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Project description:BackgroundThe p38MAPK family of Mitogen Activated Protein Kinases are a group of signalling molecules involved in cell growth, survival, proliferation and differentiation. The widely studied p38α isoform is ubiquitously expressed and is implicated in a number of cancer pathologies, as are p38γ and p38δ. However, the mechanistic role of the isoform, p38β, remains fairly elusive. Recent studies suggest a possible role of p38β in both breast and endometrial cancer with research suggesting involvement in bone metastasis and cancer cell survival. Female tissue specific cancers such as breast, endometrial, uterine and ovary account for over 3,000,000 cancer related incidents annually; advancements in therapeutics and treatment however require a deeper understanding of the molecular aetiology associated with these diseases. This study provides an overview of the MAPK signalling molecule p38β (MAPK11) in female cancers using an in-silico approach.MethodsA detailed gene expression and methylation analysis was performed using datasets from cBioportal, CanSar and MEXPRESS. Breast, Uterine Endometrial, Cervical, Ovarian and Uterine Carcinosarcoma TCGA cancer datasets were used and analysed.ResultsData using cBioportal and CanSAR suggest that expression of p38β is lower in cancers: BRCA, UCEC, UCS, CESC and OV compared to normal tissue. Methylation data from SMART and MEXPRESS indicate significant probe level variation of CpG island methylation status of the gene MAPK11. Analysis of the genes' two CpG islands shows that the gene was hypermethylated in the CpG1 with increased methylation seen in BRCA, CESC and UCEC cancer data sets with a slight increase of expression recorded in cancer samples. CpG2 exhibited hypomethylation with no significant difference between samples and high levels of expression. Further analysis from MEXPRESS revealed no significance between probe methylation and altered levels of expression. In addition, no difference in the expression of BRCA oestrogen/progesterone/HER2 status was seen.ConclusionThis data provides an overview of the expression of p38β in female tissue specific cancers, showing a decrease in expression of the gene in BRCA, UCEC, CESC, UCS and OV, increasing the understanding of p38β MAPK expression and offering insight for future in-vitro investigation and therapeutic application.

Dataset Information

P38? and Cancer: The Beginning of the Road.

Publications

p38β and Cancer: The Beginning of the Road.

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