Chaudhary Nidhee, Kiranmayee Bellam
Centre for Biotechnology & Biochemical Engineering, Amity Institute Biotechnology, Amity University Uttar Pradesh, Sector-125, Expressway, Noida, 201313, Uttar Pradesh, India.
Curr Pharm Biotechnol. 2025;26(5):654-664. doi: 10.2174/0113892010288624240213072415.
The role of non-receptor type Protein Tyrosine Phosphatase (PTPases) in controlling pathways related to diabetes and Hepatocellular Carcinoma (HCC) is significant. The insulin signal transduction pathway is regulated by the steady-state phosphorylation of tyrosyl residues of the insulin receptor and post-receptor substrates. PTPase has been shown to have a physiological role in the regulation of reversible tyrosine phosphorylation. There are several non-receptor type PTPases. PTPase containing the SH-2 domain (SHP-2) and the non-receptor type PTPase (PTP1B; encoded by the PTPN1 gene) are involved in negative regulation of the insulin signaling pathway, thereby indicating that the pathway can be made more efficient by the reduction in the activity of specific PTPases. Reduction in insulin resistance may be achieved by drugs targeting these specific enzymes. The modifications in the receptor and post-receptor events of insulin signal transduction give rise to insulin resistance, and a link between insulin-resistant states and HCC has been established. The cancer cells thrive on higher levels of energy and their growth gets encouraged since insulin-resistant states lead to greater glucose levels. Cancer, hyperglycemia, and hypoglycemia are highly linked through various pathways hence, clarifying the molecular mechanisms through which non-receptor type PTPase regulates the insulin signal transduction is necessary to find an effective target for cancer. Targeting the pathways related to PTPases; both receptor and non-receptor types, may lead to an effective candidate to fight against diabetes and HCC.
非受体型蛋白酪氨酸磷酸酶(PTPases)在控制与糖尿病和肝细胞癌(HCC)相关的信号通路中发挥着重要作用。胰岛素信号转导通路受胰岛素受体及受体后底物酪氨酸残基的稳态磷酸化调节。PTPase已被证明在可逆性酪氨酸磷酸化的调节中具有生理作用。存在多种非受体型PTPases。含SH-2结构域的PTPase(SHP-2)和非受体型PTPase(PTP1B;由PTPN1基因编码)参与胰岛素信号通路的负调控,这表明通过降低特定PTPases的活性可提高该通路的效率。通过靶向这些特定酶的药物可能实现胰岛素抵抗的降低。胰岛素信号转导中受体及受体后事件的改变会导致胰岛素抵抗,并且胰岛素抵抗状态与HCC之间的联系已被确立。癌细胞在较高能量水平下茁壮成长,且由于胰岛素抵抗状态导致更高的葡萄糖水平,其生长受到促进。癌症、高血糖和低血糖通过各种途径高度相关,因此,阐明非受体型PTPase调节胰岛素信号转导的分子机制对于找到有效的癌症治疗靶点至关重要。靶向与PTPases相关的信号通路,包括受体型和非受体型,可能会产生对抗糖尿病和HCC的有效候选药物。