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PlexinA1 activation induced by β2-AR promotes epithelial-mesenchymal transition through JAK-STAT3 signaling in human gastric cancer cells.


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.

SUBMITTER: Liu Y 

PROVIDER: S-EPMC9066200 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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PlexinA1 activation induced by β2-AR promotes epithelial-mesenchymal transition through JAK-STAT3 signaling in human gastric cancer cells.

Liu Ying Y   Hao Yanhui Y   Zhao Hanzheng H   Zhang Ying Y   Cheng Die D   Zhao Li L   Peng Yuqiao Y   Lu Yanjie Y   Li Yuhong Y  

Journal of Cancer 20220418 7


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 mec  ...[more]

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