ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2024; 15(5):1355-1365. doi:10.7150/jca.83812 This issue Cite
Research Paper
SP1 Mediated PIK3CB Upregulation Promotes Gastric Carcinogenesis
1. Department of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China.
2. Research Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China.
Abstract
PIK3CB, one of catalytic subunits of PI3Ks kinase family, is implicated in several cellular processes such as cell growth, proliferation, mobility and neoplastic transformation. Its abnormal expression has been found in several human cancer types. However, the regulation pattern and function of PIK3CB in gastric cancer (GC) are still unclear. Here, we demonstrated that PIK3CB and SP1 (special protein 1) were both upregulated in GC samples compared to adjacent non-cancerous stomach tissues at mRNA and protein levels. The expression of the two genes also displayed a significant positive correlation in GC samples. Dual-luciferase assays and chromatin immunoprecipitation (ChIP) assays revealed that SP1 could bind to the -771~-605 region of the promoter of PIK3CB and enhance transcription. Furthermore, we discovered that SP1 induced AKT activation through PIK3CB and accelerated GC cell proliferation and migration in a PIK3CB/AKT signaling dependent manner. TGX-221, a PIK3CB-selective inhibitor, which can block this signaling transduction pathway, was found to inhibit the growth of GC cells and induce apoptosis in vitro, implying that it may act as a potential development agent for GC. These collective findings provide a new insight into PI3K/AKT signaling that SP1 may function as an upstream factor on PI3K, forming a new signaling axis to promote the progression of GC or other malignancies.
Keywords: SP1, PIK3CB, Gastric cancer, AKT, TGX-221
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