Central Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
School of Biology and Basic Medical Sciences, Medical College, Soochow University, Suzhou, Jiangsu, China.
Neoplasma. 2022 Jul;69(4):859-867. doi: 10.4149/neo_2022_211009N1427. Epub 2022 May 9.
Transmembrane-4 L Six Family member 1 (TM4SF1) belongs to a family of integral membrane proteins implicated in cell growth and tumor progression. Glioma is the most common and aggressive malignant brain tumor in adults. In this study, we showed that TM4SF1 was highly expressed in glioma tumor tissues and cell lines. The expression levels of TM4SF1 were negatively correlated with patients' survival rates. Silencing TM4SF1 by RNA interference inhibited the proliferation, migration, and invasion of glioma cells. Moreover, TM4SF1 silencing induced glioma cell cycle arrest and early apoptosis. In contrast, overexpression of TM4SF1 in glioma cells exhibited the opposite effects. Mechanistically, we found that loss of TM4SF1 reduced phospho-ATK, Cyclin D1, Bcl-2, and MMP-9 levels in glioma cells. Taken together, these findings provide novel insights into glioma pathogenesis and suggest that TM4SF1 may represent a novel target for glioma intervention.
跨膜 4 L 六家族成员 1(TM4SF1)属于整联蛋白家族,与细胞生长和肿瘤进展有关。神经胶质瘤是成人中最常见且侵袭性最强的恶性脑肿瘤。在这项研究中,我们表明 TM4SF1 在神经胶质瘤肿瘤组织和细胞系中高度表达。TM4SF1 的表达水平与患者的生存率呈负相关。通过 RNA 干扰沉默 TM4SF1 抑制了神经胶质瘤细胞的增殖、迁移和侵袭。此外,TM4SF1 沉默诱导神经胶质瘤细胞周期停滞和早期凋亡。相反,在神经胶质瘤细胞中过表达 TM4SF1 则表现出相反的效果。从机制上讲,我们发现 TM4SF1 的缺失降低了神经胶质瘤细胞中磷酸化 ATK、Cyclin D1、Bcl-2 和 MMP-9 的水平。总之,这些发现为神经胶质瘤的发病机制提供了新的见解,并表明 TM4SF1 可能成为神经胶质瘤干预的新靶点。