@Article{or.2023.029698,
AUTHOR = {JUNYU HE, FENG ZENG, XI JIN, LIN LIANG, MENGXIANG GAO, WENTAO LI, GUIYUAN LI, YANHONG ZHOU},
TITLE = {YWHAH activates the HMGA1/PI3K/AKT/mTOR signaling pathway by positively regulating Fra-1 to affect the proliferation of gastric cancer cells},
JOURNAL = {Oncology Research},
VOLUME = {31},
YEAR = {2023},
NUMBER = {4},
PAGES = {615--630},
URL = {http://www.techscience.com/or/v31n4/53325},
ISSN = {1555-3906},
ABSTRACT = {Fos-related antigen 1 (Fra-1) is a nuclear transcription factor that regulates cell growth, differentiation, and apoptosis. It is involved in the proliferation, invasion, apoptosis and epithelial mesenchymal transformation of malignant tumor cells. Fra-1 is highly expressed in gastric cancer (GC), affects the cycle distribution and apoptosis of GC cells, and participates in GC occurrence and development. However, the detailed mechanism of Fra-1 in GC is unclear, such as the identification of Fra-1-interacting proteins and their role in GC pathogenesis. In this study, we identified tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH) as a Fra-1-interacting protein in GC cells using co-immunoprecipitation combined with liquid chromatography-tandem mass spectrometry. Experiments showed that YWHAH positively regulated Fra-1 mRNA and protein expression, and affected GC cell proliferation. Whole proteome analysis showed that Fra-1 affected the activity of the high mobility group AT-hook 1 (HMGA1)/phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway in GC cells. Western blotting and flow cytometry confirmed that YWHAH activated HMGA1/PI3K/AKT/mTOR signaling pathway by positively regulating Fra-1 to affect GC cell proliferation. These results will help to discover new molecular targets for the early diagnosis, treatment, and prognosis prediction of GC.},
DOI = {10.32604/or.2023.029698}
}