Impact of p38γ mitogen-activated protein kinase (MAPK) on MDA-MB-231 breast cancer cells using metabolomic approach

Chen, Hongshen; Wang, Xin; Guo, Fangdong; Li, Pi-Song; Peng, Dashuai; He, Jing

doi:10.1016/j.biocel.2018.11.002

Cited by 7 publications

(5 citation statements)

References 29 publications

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“…Simultaneously, MAPK12 and MAPK13 have 70% similarity with each other [ 43 ]. The role in cell apoptosis, invasion, and migration of MAPK12 has been proved through a new metabolomic approach [ 44 ]. Hence, HPC may activate the MAPK signaling pathway through different pathways to regulate the proliferation of GCs, and we selected MAPK12 , which is the most differentially expressed gene in regulating ovarian GCs with HPC.…”

Section: Discussionmentioning

confidence: 99%

Prolactin Regulates Ovine Ovarian Granulosa Cell Apoptosis by Affecting the Expression of MAPK12 Gene

Yang

Duan

Zhang

et al. 2023

IJMS

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Prolactin (PRL) has been reported to influence reproductive performance and cell apoptosis. However, its mechanism remains unclear. Hence, in the present study, ovine ovarian granulosa cells (GCs) were used as a cell model to investigate the relationship between PRL concentration and GC apoptosis, as well as its possible mechanisms. We examined the relationship between serum PRL concentration and follicle counts in sexually mature ewes. GCs were isolated from adult ewes and treated with different concentrations of PRL, while 500 ng/mL PRL was selected as the high concentration of prolactin (HPC). Then, we applied the transcriptome sequencing (RNA-Seq) combined with a gene editing approach to explore the HPC contributing to cell apoptosis and steroid hormones. The apoptosis of GCs gradually increased at PRL concentrations above 20 ng/mL, while 500 ng/mL PRL significantly decreased the secretion of steroid hormones and the expression of L-PRLR and S-PRLR. The results indicated that PRL regulates GC development and steroid hormones mainly through the target gene MAPK12. The expression of MAPK12 was increased after knocked-down L-PRLR and S-PRLR, while it decreased after overexpressed L-PRLR and S-PRLR. Cell apoptosis was inhibited and the secretion of steroid hormones increased after interfering with MAPK12, while the overexpression of MAPK12 showed the opposite trend. Overall, the number of follicles gradually decreased with increasing PRL concentration. HPCs promoted apoptosis and inhibited steroid hormone secretion in GCs by upregulating MAPK12 through reducing L-PRLR and S-PRLR.

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Section: Discussionmentioning

confidence: 99%

Prolactin Regulates Ovine Ovarian Granulosa Cell Apoptosis by Affecting the Expression of MAPK12 Gene

Yang

Duan

Zhang

et al. 2023

IJMS

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“…These results indicate that p38γ can promote glucose uptake in different tissues via different glucose transporters. p38γ also activates metabolic pathways in 231 human breast cancer cells as demonstrated by both knockdown and overexpression [ 43 ]. These studies together demonstrate a critical role of p38γ in diabetes and cancer by regulation of glucose-associated metabolic signaling.…”

Section: P38γ Signaling In Metabolismmentioning

confidence: 99%

p38γ MAPK Inflammatory and Metabolic Signaling in Physiology and Disease

Chen

2023

Cells

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p38γ MAPK (also called ERK6 or SAPK3) is a family member of stress-activated MAPKs and has common and specific roles as compared to other p38 proteins in signal transduction. Recent studies showed that, in addition to inflammation, p38γ metabolic signaling is involved in physiological exercise and in pathogenesis of cancer, diabetes, and Alzheimer’s disease, indicating its potential as a therapeutic target. p38γphosphorylates at least 19 substrates through which p38γ activity is further modified to regulate life-important cellular processes such as proliferation, differentiation, cell death, and transformation, thereby impacting biological outcomes of p38γ-driven pathogenesis. P38γ signaling is characterized by its unique reciprocal regulation with its specific phosphatase PTPH1 and by its direct binding to promoter DNAs, leading to transcriptional activation of targets including cancer-like stem cell drivers. This paper will review recent findings about p38γ inflammation and metabolic signaling in physiology and diseases. Moreover, we will discuss the progress in the development of p38γ-specific pharmacological inhibitors for therapeutic intervention in disease prevention and treatment by targeting the p38γ signaling network.

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“…Involvement in cellular metabolism is another mechanism by which p38γ increases BC invasiveness. Using a novel metabolomics approach to demonstrate the role of p38γ in apoptosis, invasion, and migration, Chen et al showed the potential to promote cancer metastasis, particularly altering the enrichment of certain metabolites and metabolic pathways, which may bring potential to the evolution of novel therapeutic strategies for BC [40].…”

Section: Breast Cancermentioning

confidence: 99%

The Role of p38γ in Cancer: From review to outlook

Xu¹,

Li²,

Dai³

et al. 2021

Int. J. Biol. Sci.

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p38γ is a member of the p38 Mitogen Activated Protein Kinases (p38 MAPKs). It contains four subtypes in mammalian cells encoded by different genes including p38α (MAPK14), p38β (MAPK11), p38γ (MAPK12), and p38δ (MAPK13). Recent studies revealed that p38γ may exhibit a crucial role in tumorigenesis and cancer aggressiveness. Despite the large number of published literatures, further researches are demanded to clarify its role in cancer development, the tissue-specific function and associated novel treatment strategies. In this article, we provide the latest view on the connection between p38γ and malignant tumors, highlighting the function of p38γ. The clinical value of p38γ is also discussed, helping the translation into the remarkable therapeutic strategy in tumor diseases.

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Impact of p38γ mitogen-activated protein kinase (MAPK) on MDA-MB-231 breast cancer cells using metabolomic approach

Cited by 7 publications

References 29 publications

Prolactin Regulates Ovine Ovarian Granulosa Cell Apoptosis by Affecting the Expression of MAPK12 Gene

Prolactin Regulates Ovine Ovarian Granulosa Cell Apoptosis by Affecting the Expression of MAPK12 Gene

p38γ MAPK Inflammatory and Metabolic Signaling in Physiology and Disease

The Role of p38γ in Cancer: From review to outlook

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