Ma Jianxing, Sun Fengyao, Li Wen, Du Ruihang, Liu Mingchan, Wei Qiuya, Kang Boxiong, Yan Siyuan, Wang Chen
Department of General Surgery, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730000, China.
Precision Medicine Laboratory for Chronic Non-Communicable Diseases of Shandong Province, Institute of Precision Medicine, Jining Medical University, Jining, 272067, China.
J Transl Med. 2024 Dec 2;22(1):1093. doi: 10.1186/s12967-024-05910-4.
Sulfotransferase family 2B member 1 (SULT2B1) is involved in regulating cell proliferation, migration and metabolism. However, there is still dispute regarding whether SULT2B1 acts as an oncogene or a suppressor, and the intrinsic mechanisms in modulating tumor progression need to be further elucidated.
This work aims to reveal the relationship among SULT2B1, AKT, PKM2 signaling and glycolytic pathways, and provided a theoretical basis for SULT2B1 as a potential therapeutic target for CRC.Bioinformatics methods, immunohistochemistry (IHC) and immunoblotting assays were performed to analyze the correlation between SULT2B1 and colorectal cancer (CRC). The effect of SULT2B1 on cell proliferation and migration were investigated by several phenotypic experiments in vitro and animal studies. The SULT2B1 interacting proteins were determined by immunofluorescence, immunoprecipitation and GST-pull down assays. Immunoblotting and mCherry-GFP-LC3 assays were performed to analysis autophagy. Chromatin immunoprecipitation (CHIP) assay was utilized to detect the effect of SULT2B1 in regulating transcription. Small molecule agonist/antagonist was used to modify protein activity and therefore analyze the mutual relationships.
SULT2B1 is a predictive biomarker that is abnormally overexpressed in CRC tissues. Overexpression of SULT2B1 promoted cell proliferation and migration, while its knockout suppressed these processes. Furthermore, SULT2B1 could directly interact with the oncogene AKT and thereby enhance the activity of AKT-mTORC1 signaling. Furthermore, PKM2 was found to bind with SULT2B1, and regulated by SULT2B1 at both transcription and degradation levels. Moreover, blocking glycolysis attenuated the promoting effect of OE-SULT2B1.
SULT2B1 acts as an oncogene in CRC via modulating the AKT/PKM2 axis, therefore making it a promising diagnostic and therapeutic target for CRC.
磺基转移酶家族2B成员1（SULT2B1）参与调节细胞增殖、迁移和代谢。然而，关于SULT2B1是作为癌基因还是抑癌基因仍存在争议，调节肿瘤进展的内在机制有待进一步阐明。
本研究旨在揭示SULT2B1、AKT、PKM2信号传导与糖酵解途径之间的关系，为SULT2B1作为结直肠癌潜在治疗靶点提供理论依据。采用生物信息学方法、免疫组织化学（IHC）和免疫印迹分析SULT2B1与结直肠癌（CRC）的相关性。通过体外和动物实验的多种表型实验研究SULT2B1对细胞增殖和迁移的影响。通过免疫荧光、免疫沉淀和GST下拉实验确定SULT2B1相互作用蛋白。进行免疫印迹和mCherry-GFP-LC3实验分析自噬。利用染色质免疫沉淀（CHIP）实验检测SULT2B1对转录的调节作用。使用小分子激动剂/拮抗剂修饰蛋白活性，进而分析相互关系。
SULT2B1是一种预测性生物标志物，在CRC组织中异常高表达。SULT2B1的过表达促进细胞增殖和迁移，而其敲除则抑制这些过程。此外，SULT2B1可直接与癌基因AKT相互作用，从而增强AKT-mTORC1信号传导的活性。此外，发现PKM2与SULT2B1结合，并在转录和降解水平上受SULT2B1调控。此外，阻断糖酵解可减弱OE-SULT2B1的促进作用。
SULT2B1通过调节AKT/PKM2轴在CRC中发挥癌基因作用，因此使其成为CRC有前景的诊断和治疗靶点。
