Mapk14, also known as p38α, is a pivotal component of the p38 mitogen-activated protein kinase (MAPK) signaling pathway. This pathway is associated with multiple disease states such as inflammatory disorders, neurodegenerative diseases, cardiovascular cases, and cancer [2].

In the context of prolactinoma, gene knockout studies in mice models (estradiol-induced and dopamine D2 receptor knockout mice) demonstrated that Mapk14 knockout significantly inhibited tumor overgrowth and decreased prolactin (PRL) expression. This indicates that Mapk14 promotes the formation of prolactinoma [1].

In polycythemia vera (PV), Mapk14 over-expression was identified as a transcriptomic feature. Genome-scale correlation analysis revealed its association with JAK/STAT family genes, and patients with high Mapk14 expression had more adverse clinical outcomes [3].

In gastric cancer, high levels of Mapk14 were found in advanced stages, and inhibition of Mapk14 (p38α) impaired cell proliferation, induced apoptosis, and inhibited cell migration, suggesting it could be a potential biomarker and pharmacological target [4].

In endometrial cancer, Mapk14 was identified as a specific requirement for high-grade endometrial carcinoma (HGEC) in spheroid culture, promoting tumorigenicity in vivo [5].

In conclusion, Mapk14 is crucial in the p38 MAPK signaling pathway, playing significant roles in various diseases. Gene knockout models in mice have been instrumental in revealing its promoting effects in prolactinoma, its association with adverse outcomes in PV, and its potential as a biomarker and target in gastric and endometrial cancers. These findings enhance our understanding of disease mechanisms and suggest potential therapeutic strategies targeting Mapk14.

References:

1. Ding, Qiao-Yan, Zhang, Yu, Ma, Li, Zhang, Hong-Feng, Wang, Xiong. 2020. Inhibiting MAPK14 showed anti-prolactinoma effect. In BMC endocrine disorders, 20, 138. doi:10.1186/s12902-020-00619-z. https://pubmed.ncbi.nlm.nih.gov/32894113/

2. Madkour, Moustafa M, Anbar, Hanan S, El-Gamal, Mohammed I. 2021. Current status and future prospects of p38α/MAPK14 kinase and its inhibitors. In European journal of medicinal chemistry, 213, 113216. doi:10.1016/j.ejmech.2021.113216. https://pubmed.ncbi.nlm.nih.gov/33524689/

3. Guo, Chao, Gao, Ya-Yue, Ju, Qian-Qian, Gong, Ming, Li, Zhen-Ling. 2021. MAPK14 over-expression is a transcriptomic feature of polycythemia vera and correlates with adverse clinical outcomes. In Journal of translational medicine, 19, 233. doi:10.1186/s12967-021-02913-3. https://pubmed.ncbi.nlm.nih.gov/34059095/

4. Mesquita, Felipe Pantoja, Moreira-Nunes, Caroline Aquino, da Silva, Emerson Lucena, de Moraes, Maria Elisabete Amaral, Montenegro, Raquel Carvalho. 2020. MAPK14 (p38α) inhibition effects against metastatic gastric cancer cells: A potential biomarker and pharmacological target. In Toxicology in vitro : an international journal published in association with BIBRA, 66, 104839. doi:10.1016/j.tiv.2020.104839. https://pubmed.ncbi.nlm.nih.gov/32243890/

5. Joseph, Sayali, Zhang, Xingyuan, Droby, Gaith N, Bowser, Jessica L, Vaziri, Cyrus. 2024. MAPK14/p38α shapes the molecular landscape of endometrial cancer and promotes tumorigenic characteristics. In Cell reports, 44, 115104. doi:10.1016/j.celrep.2024.115104. https://pubmed.ncbi.nlm.nih.gov/39708320/