Department of Pathology, Affiliated Hospital of Southwest Medical University, Luzhou, 646099, China.
Clinical Skills Center of Affiliated Hospital of Southwest Medical University, Luzhou, 646099, China.
Curr Med Sci. 2022 Aug;42(4):733-741. doi: 10.1007/s11596-022-2606-4. Epub 2022 Jul 7.
Arginine ADP-ribosyltransferase 1 (ART1) is involved in the regulation of a diverse array of pathophysiological processes, including proliferation, invasion, apoptosis, autophagy and angiogenesis of colorectal cancer (CRC) cells. However, how ART1 regulates glycolysis in CRC remains elusive.
To elucidate the role of ART1 in glycolysis in CRC, we assessed the protein level of ART1, hypoxia-inducible factor 1α (HIF1α), and glucose transporter type 1 (GLUT1) in 61 CRC tumor tissue specimens obtained from patients with different 2-[F]fluoro-2-deoxy-D-glucose (F-FDG) uptake as analyzed by PET/CT before surgery. Colon adenocarcinoma CT26 cells with ART1 knockdown and overexpression were established, respectively, and the molecular mechanism underlying the effect of ART1 on glycolysis in CRC was determined both in vivo and in vitro.
The expression of ART1 and GLUT1 was significantly associated with FDG uptake (P=0.037 and P=0.022, respectively) in CRC tissues. Furthermore, the expression of hexokinase 2 (HK2) and lactate dehydrogenase (LDH) was upregulated in ART1-overexpressed CT26 cells, but was downregulated in ART1-knockdown CT26 cells. The volume and weight of subcutaneously transplanted tumors were markedly increased in the ART1-overexpressed BALB/c mice group and decreased in the ART1-knockdown group. In CT26 cells, the overexpression of ART1 promoted the expression levels of HK2 and LDH, and knockdown of ART1 suppressed them in the CT26 tumors. In both normal and hypoxic conditions, ART1 expression was associated with the protein level of phospho-serine/threonine kinase (p-AKT), HIF1α, and GLUT1 but not with that of AKT in CT26 cells and subcutaneous transplanted tumors.
ART1 plays a crucial role in the elevation of glucose consumption in CT26 cells and may regulate GLUT1-dependent glycolysis in CRC via the PI3K/AKT/HIF1α pathway.
精氨酸 ADP-核糖基转移酶 1（ART1）参与调节多种病理生理过程，包括结直肠癌细胞（CRC）的增殖、侵袭、凋亡、自噬和血管生成。然而，ART1 如何调节 CRC 中的糖酵解仍不清楚。
为了阐明 ART1 在 CRC 中糖酵解中的作用，我们评估了 61 例 CRC 肿瘤组织标本中 ART1、缺氧诱导因子 1α（HIF1α）和葡萄糖转运蛋白 1（GLUT1）的蛋白水平，这些标本是根据手术前 PET/CT 分析获得的不同 2-[F]氟-2-脱氧-D-葡萄糖（F-FDG）摄取情况获得的。分别建立了 ART1 敲低和过表达的结肠腺癌 CT26 细胞，并在体内和体外确定了 ART1 对 CRC 中糖酵解的影响的分子机制。
ART1 和 GLUT1 的表达与 CRC 组织中的 FDG 摄取显著相关（P=0.037 和 P=0.022）。此外，在 ART1 过表达的 CT26 细胞中，己糖激酶 2（HK2）和乳酸脱氢酶（LDH）的表达上调，而在 ART1 敲低的 CT26 细胞中表达下调。在 ART1 过表达的 BALB/c 小鼠组中，皮下移植瘤的体积和重量明显增加，而在 ART1 敲低组中则减少。在 CT26 细胞中，ART1 的过表达促进了 HK2 和 LDH 的表达水平，而在 CT26 肿瘤中敲低 ART1 则抑制了它们的表达。在正常和缺氧条件下，ART1 表达与 CT26 细胞和皮下移植瘤中磷酸丝氨酸/苏氨酸激酶（p-AKT）、HIF1α 和 GLUT1 的蛋白水平相关，但与 AKT 的蛋白水平无关。
ART1 在 CT26 细胞葡萄糖消耗的升高中发挥关键作用，可能通过 PI3K/AKT/HIF1α 途径调节 CRC 中 GLUT1 依赖性糖酵解。
