ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2022; 13(7):2258-2270. doi:10.7150/jca.70000 This issue Cite
Research Paper
PlexinA1 activation induced by β2-AR promotes epithelial-mesenchymal transition through JAK-STAT3 signaling in human gastric cancer cells
1. Department of Pathology, Chengde Medical University, Chengde, Hebei, China.
2. Cancer Research Laboratory, Chengde Medical College, Chengde, Hebei, China.
3. Beijing Institute of Radiation Medicine, Beijing, China.
4. Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
5. Department of clinical laboratory, The First Affiliated Hospital of Chengde Medical College, Chengde, Hebei, China.
6. Department of Ultrasound Medicine, The First Affiliated Hospital of Chengde Medical College, Chengde, Hebei, China.
#These authors have contributed equally to this work and share first authorship.
Abstract
With the medical model shifting from a single biomedical model to a biopsychological-social model, the impact of psychosocial factors on cancer patients has attracted attention. Studies have shown that chronic stress caused by long-term psychological stress, such as anxiety and depression, can promote the malignant progression of tumors by acting on β2-adrenergic receptor (β2-AR). β2-AR can promote tumor migration by activating epithelial-mesenchymal transition (EMT). However, the underlying mechanisms in the regulation of EMT by β2-AR are still unclear. In this study, we established a chronic stress model by treating MGC-803 and SGC-7901 human gastric cancer cells with isoproterenol (ISO), a β2-AR agonist. EMT in the two gastric cancer cell lines was enhanced after ISO treatment. Thereafter, we found that the interaction between β2-AR and PlexinA1 was involved in the process by which chronic stress affects EMT in both MGC-803 and SGC-7901 cells. Moreover, the activation of β2-AR by ISO increased the expression of PlexinA1, activated JAK-STAT3 signaling and further promoted EMT in human gastric cancer cells. Importantly, the knockdown of PlexinA1 by small hairpin RNAs inhibited JAK-STAT3 signaling and abolished the EMT induced by β2-AR. In conclusion, PlexinA1 was an important downstream target of β2-AR, through which β2-AR promoted EMT in human gastric cancer cells by activating JAK-STAT3 signaling.
Keywords: gastric cancer, chronic stress, epithelial-mesenchymal transition, β2-AR, PlexinA1, JAK-STAT3
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