Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550001, Guizhou, China.
Clinical Research Center, Affiliated Hospital of Guizhou Medical University, Guiyang, 550001, Guizhou, China.
Med Oncol. 2023 Jul 31;40(9):257. doi: 10.1007/s12032-023-02127-1.
Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) has been reported to be a new tumor suppressor with a significant inhibitory effect in various cancers. Although LHPP has been repeatedly shown to inhibit the progression of various tumors by inhibiting the phosphorylation of AKT, up to now, the studies on the function and mechanism of LHPP in tumors are insufficient. In this study, LHPP expression was found to be downregulated in both hepatocellular carcinoma (HCC) and pancreatic cancer (PC). Here, we found that LHPP could bind to epidermal growth factor receptor (EGFR) and inhibit its phosphorylation, which thereby inhibited the activation of EGFR downstream pathways ERK, AKT, and STAT3, and then weakening the ability to proliferate, invade, and migrate in HCC and PC. This paper showed a new physiological function of LHPP in inhibiting phosphorylation of EGFR and its potential anti-tumor mechanism and indicated that LHPP was a potential therapeutic target for HCC and PC.
磷酸丝氨酸磷酸组氨酸无机焦磷酸酶 (LHPP) 已被报道为一种新的肿瘤抑制因子，对各种癌症具有显著的抑制作用。尽管 LHPP 已被反复证明通过抑制 AKT 的磷酸化来抑制各种肿瘤的进展，但到目前为止，关于 LHPP 在肿瘤中的功能和机制的研究还不够充分。在本研究中，发现 LHPP 在肝细胞癌 (HCC) 和胰腺癌 (PC) 中均下调表达。在这里，我们发现 LHPP 可以与表皮生长因子受体 (EGFR) 结合并抑制其磷酸化，从而抑制 EGFR 下游通路 ERK、AKT 和 STAT3 的激活，进而削弱 HCC 和 PC 中增殖、侵袭和迁移的能力。本文展示了 LHPP 在抑制 EGFR 磷酸化及其潜在抗肿瘤机制方面的新生理功能，并表明 LHPP 是 HCC 和 PC 的潜在治疗靶点。
