文章：

ITGA3通过依赖胶原I的自分泌方式，在HIF1α和c-Myc驱动的糖酵解作用下促进胰腺癌进展

ITGA3 promotes pancreatic cancer progression through HIF1α- and c-Myc-driven glycolysis in a collagen I-dependent autocrine manner 

原文发布日期：2024-12-17 

英文摘要：

Pancreatic cancer is characterized by severe metabolic stress due to its prominent desmoplasia and poor vascularization. Integrin subunit alpha 3 (ITGA3) is a cell surface adhesion protein involved in tumor progression. However, the role of ITGA3 in pancreatic cancer progression, especially in metabolic reprogramming, remains largely unknown. In this study, we found that ITGA3 expression is elevated in pancreatic cancer tissues and predicts poor prognosis for patients with pancreatic cancer. Functional assays revealed that ITGA3 promotes the growth and liver metastasis of pancreatic cancer via boosting glycolysis. Mechanistically, Collagen I (Col1) derived from cancer cells acts as a ligand for ITGA3 to activate the FAK/PI3K/AKT/mTOR signaling pathway in an autocrine manner, thereby increasing the expression of HIF1α and c-Myc, two critical regulators of glycolysis. Blockade of Col1 by siRNA or of ITGA3 by a blocking antibody leads to specific inactivation of the FAK/PI3K/AKT/mTOR pathway and impairs malignant tumor behaviors induced by ITGA3. Thus, our data indicate that ITGA3 enhances glycolysis to promote pancreatic cancer growth and metastasis via increasing HIF1α and c-Myc expression in a Col1-dependent autocrine manner, making ITGA3 as a candidate diagnostic biomarker and a potential therapeutic target for pancreatic cancer. 

摘要翻译：

胰腺癌因其显著的纤维增生和不良血管化而具有严重的代谢应激特征。整合素亚基α3（ITGA3）是一种参与肿瘤进展的细胞表面粘附蛋白。然而，ITGA3在胰腺癌进展中的作用，特别是在代谢重编程方面，仍 largely 未知。本研究发现ITGA3在胰腺癌组织中表达升高，并预示患者不良预后。功能实验显示ITGA3通过增强糖酵解促进胰腺癌的生长和肝转移。机制上，癌细胞来源的胶原蛋白I（Col1）作为ITGA3的配体以自分泌方式激活FAK/PI3K/AKT/mTOR信号通路，从而增加糖酵解两个关键调控因子HIF1α和c-Myc的表达。通过siRNA阻断Col1或使用阻断抗体抑制ITGA3，可特异性灭活FAK/PI3K/AKT/mTOR通路并削弱ITGA3诱导的恶性肿瘤行为。因此，我们的数据表明ITGA3通过Col1依赖的自分泌方式增强HIF1α和c-Myc表达，进而促进糖酵解以驱动胰腺癌生长和转移，这使得ITGA3成为胰腺癌潜在的诊断生物标志物和治疗靶点。

原文链接：

ITGA3 promotes pancreatic cancer progression through HIF1α- and c-Myc-driven glycolysis in a collagen I-dependent autocrine manner