PTPRH promotes the progression of non-small cell lung cancer via glycolysis mediated by the PI3K/AKT/mTOR signaling pathway.
PTPRH promotes the progression of non-small cell lung cancer via glycolysis mediated by the PI3K/AKT/mTOR signaling pathway.
复制标题
PTPRH通过PI 3 K/AKT/mTOR信号通路介导的糖酵解促进非小细胞肺癌的进展。
DOI：
10.1186/s12967-023-04703-5
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发表时间：
2023-11-16
影响因子：
7.4
通讯作者：
Li, Yaming
中科院分区：
文献类型：
--
作者：
Wang, Shu;Cheng, Zhiming;Cui, Yan;Xu, Shuoyan;Luan, Qiu;Jing, Shan;Du, Bulin;Li, Xuena;Li, Yaming
关键词：
蛋白酪氨酸磷酸酶H受体（PTPRH）是已知的调节胰腺癌和结直肠癌的发生和发展。然而，其与非小细胞肺癌（NSCLC）中糖酵解的关系仍不清楚。在这项研究中，我们的目的是研究PTPRH表达和葡萄糖代谢之间的关系和潜在的作用机制。采用免疫组化染色、qRT-PCR和Western blotting检测PTPRH在NSCLC细胞中的表达。通过集落形成实验、EdU实验、Transwell实验、伤口愈合实验和流式细胞术评价PTPRH对细胞生物学行为的影响。通过γ计数器和乳酸试验检测改变PTPRH表达后F-18-氟脱氧葡萄糖（18F-FDG）摄取和葡萄糖代谢产物水平的变化。Western blotting检测PTPRH表达改变后NSCLC细胞糖酵解相关蛋白的表达。结果显示PTPRH在临床患者组织标本中呈高表达，且与肿瘤直径及临床分期密切相关。PTPRH表达与18F-FDG正电子发射断层扫描/计算机断层扫描（PET/CT）显示的糖代谢指数、Ki 67表达水平和糖酵解相关蛋白表达水平相关。PTPRH改变细胞行为，抑制细胞凋亡，促进18F-FDG摄取，乳酸产生和糖酵解相关蛋白的表达。此外，PTPRH通过磷脂酰肌醇-3-激酶（PI 3 K）/蛋白激酶B（AKT）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路调节NSCLC细胞的糖代谢，使用LY 294002和740 Y-P（分别为PI 3 K的抑制剂和激动剂）进行评估。使用裸鼠中的异种移植肿瘤模型在体内验证了相同的结果。使用裸鼠皮下异种移植模型，通过IHC染色测量PTPRH、糖酵解相关蛋白、p-PI 3 K/PI 3 K和p-AKT/AKT的蛋白表达水平。总之，我们报告PTPRH通过PI 3 K/AKT/mTOR信号通路促进非小细胞肺癌的糖酵解、增殖、迁移和侵袭，并最终促进肿瘤进展，这可以通过LY 294002和740 Y-P调节。这些结果表明PTPRH是非小细胞肺癌的潜在治疗靶点。在线版本包含补充材料，可通过10.1186/s12967-023-04703-5获得。
The protein tyrosine phosphatase H receptor (PTPRH) is known to regulate the occurrence and development of pancreatic and colorectal cancer. However, its association with glycolysis in non-small cell lung cancer (NSCLC) is still unclear. In this study, we aimed to investigate the relationship between PTPRH expression and glucose metabolism and the underlying mechanism of action. The expression of PTPRH in NSCLC cells was evaluated by IHC staining, qRT‒PCR and Western blotting. The effect of PTPRH on cell biological behavior was evaluated by colony assays, EdU experiments, Transwell assays, wound healing assays and flow cytometry. Changes in F-18-fluorodeoxyglucose (18F‐FDG) uptake and glucose metabolite levels after altering PTPRH expression were detected via a gamma counter and lactic acid tests. The expression of glycolysis-related proteins in NSCLC cells was detected by Western blotting after altering PTPRH expression. The results showed that PTPRH was highly expressed in clinical patient tissue samples and closely related to tumor diameter and clinical stage. In addition, PTPRH expression was associated with glycometabolism indexes on 18F-FDG positron emission tomography/computed tomography (PET/CT) imaging, the expression level of Ki67 and the expression levels of glycolysis-related proteins. PTPRH altered cell behavior, inhibited apoptosis, and promoted 18F-FDG uptake, lactate production, and the expression of glycolysis-related proteins. In addition, PTPRH modulated the glycometabolism of NSCLC cells via the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, as assessed using LY294002 and 740Y-P (an inhibitor and agonist of PI3K, respectively). The same results were validated in vivo using a xenograft tumor model in nude mice. Protein expression levels of PTPRH, glycolysis-related proteins, p-PI3K/PI3K and p-AKT/AKT were measured by IHC staining using a subcutaneous xenograft model in nude mice. In summary, we report that PTPRH promotes glycolysis, proliferation, migration, and invasion via the PI3K/AKT/mTOR signaling pathway in NSCLC and ultimately promotes tumor progression, which can be regulated by LY294002 and 740Y-P. These results suggest that PTPRH is a potential therapeutic target for NSCLC. The online version contains supplementary material available at 10.1186/s12967-023-04703-5.
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DOI：
10.3390/molecules26134100
发表时间：
2021-07-05
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Iksen;Pothongsrisit S;Pongrakhananon V
通讯作者：
Pongrakhananon V
影响因子：
5.6
作者：
通讯作者：
--
影响因子：
14.5
作者：
Sharma, Dolly;Singh, Mamta;Rani, Reshma
通讯作者：
Rani, Reshma
影响因子：
13.6
作者：
Li J;Lu H;Ng PK;Pantazi A;Ip CKM;Jeong KJ;Amador B;Tran R;Tsang YH;Yang L;Song X;Dogruluk T;Ren X;Hadjipanayis A;Bristow CA;Lee S;Kucherlapati M;Parfenov M;Tang J;Seth S;Mahadeshwar HS;Mojumdar K;Zeng D;Zhang J;Protopopov A;Seidman JG;Creighton CJ;Lu Y;Sahni N;Shaw KR;Meric-Bernstam F;Futreal A;Chin L;Scott KL;Kucherlapati R;Mills GB;Liang H
通讯作者：
Liang H
影响因子：
7.4
作者：
Poomakkoth N;Issa A;Abdulrahman N;Abdelaziz SG;Mraiche F
通讯作者：
Mraiche F