Roles of p38α and p38β mitogen‑activated protein kinase isoforms in human malignant melanoma A375 cells

Wen,Su‑Ying; Cheng,Shi‑Yann; Ng,Shang‑Chuan; Aneja,Ritu; Chen,Chih‑Jung; Huang,Chih‑Yang; Kuo,Wei‑Wen

doi:10.3892/ijmm.2019.4383

Roles of p38α and p38β mitogen‑activated protein kinase isoforms in human malignant melanoma A375 cells

Authors:
- Su‑Ying Wen
- Shi‑Yann Cheng
- Shang‑Chuan Ng
- Ritu Aneja
- Chih‑Jung Chen
- Chih‑Yang Huang
- Wei‑Wen Kuo
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Affiliations: Department of Dermatology, Taipei City Hospital, Renai Branch, Taipei 106, Taiwan, R.O.C., Department of Medical Education and Research and Department of Obstetrics and Gynecology, China Medical University Beigang Hospital, Yunlin 65152, Taiwan, R.O.C., Department of Biological Science and Technology, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 404, Taiwan, R.O.C., Department of Biology, Georgia State University, Atlanta, GA 30303, USA, Division of Breast Surgery, Department of Surgery, China Medical University Hospital, Taichung 404, Taiwan, R.O.C., Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan, R.O.C.
Published online on: October 24, 2019 https://doi.org/10.3892/ijmm.2019.4383
Pages: 2123-2132
Copyright: © Wen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Skin cancer is one of the most common cancers worldwide. Melanoma accounts for ~5% of skin cancers but causes the large majority of skin cancer‑related deaths. Recent discoveries have shown that the mitogen‑activated protein kinase (MAPK) signaling pathway is critical for melanoma development and progression. Many oncogenic pathways that cause melanoma tumorigenesis have been identified, most of which are due to RAF/MEK/ERK (MAPK) pathway activation. However, the precise role of p38 remains unclear. Using specific short hairpin (sh) RNA to silence p38α and p38β, the present findings demonstrated that p38α was a crucial factor in regulating cell migration in the A375 melanoma cell line. Silencing p38α downregulated the expression of epithelial‑mesenchymal transition markers, such as matrix metallopeptidase (MMP) 2, MMP9, twist family bHLH transcription factor 1, snail family transcriptional repressor 1 and vimentin, while mesenchymal‑epithelial transition markers, such as E‑cadherin, were upregulated. Of note, the results also demonstrated that p38α silencing impaired vascular endothelial growth factor expression, which regulates tumor angiogenesis. Furthermore, p38α knockdown inhibited cell proliferation in melanoma cells. In addition, silencing p38α induced senescence‑like features, but not cell cycle arrest. Expression of the senescence markers p16, p21, p53 and β‑galactosidase was upregulated, and an increase in the number of senescence‑associated β‑galactosidase‑positive cells was observed in a p38α knockdown stable clone. However, no significant difference was found between control and p38β stable knockdown cells. Taken together, the present results suggested that p38α knockdown impaired migration and proliferation, and increased senescence, in A375 melanoma cells. However, p38β may not be involved in melanoma tumorigenesis. Therefore, targeting p38α may be a valuable approach towards inhibiting tumor growth and metastasis in patients with melanoma.

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