抑瘤因子14通过抑制转酮醇酶o - glcn酰化抑制非小细胞肺癌细胞增殖。

IF 3.5 3区 生物学 Q3 CELL BIOLOGY
Lei Ji, Maowei Zhang, Yanan Liu, Hui Zhang, Tao Luo, Ling Zhao, Wenhui Zhang, Bi Chen, Rui Chen
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引用次数: 0

摘要

抑瘤性14蛋白(ST14)是一种II型跨膜丝氨酸蛋白酶,在多种恶性肿瘤中是一个有充分证据的致癌驱动因素。矛盾的是,其在非小细胞肺癌(NSCLC)中的病理生物学功能仍未完全确定。本研究揭示了ST14之前未被认识到的肿瘤抑制作用:我们证明ST14过表达显著抑制非小细胞肺癌细胞体外增殖和体内肿瘤生长。在机制上,我们发现了一个新的ST14-转酮醇酶(TKT)调节轴,其中ST14通过翻译后修饰调节细胞代谢。具体而言,我们确定了以下内容:(i) TKT与O-GlcNAc转移酶(OGT)物理相互作用以进行功能性O-GlcNAc酰化;(ii) ST14竞争性地破坏TKT- ogt相互作用,从而消融TKT o - glcn酰化;(三)这种对TKT糖基化的抑制减弱了糖酵解通量,如葡萄糖摄取和乳酸生成减少所证明的;(iv)由此产生的代谢损伤直接抑制细胞增殖。总的来说,这些发现提供了ST14通过糖基化依赖性代谢重编程抑制非小细胞肺癌细胞增殖的第一个机制证据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Suppressor of Tumorigenicity 14 inhibits non-small cell lung cancer cell proliferation by suppressing Transketolase O-GlcNAcylation.

Suppressor of Tumorigenicity 14 Protein (ST14), a type II transmembrane serine protease, is a well-documented oncogenic driver in multiple malignancies. Paradoxically, its pathobiological functions in non-small cell lung cancer (NSCLC) remain incompletely defined. This study uncovers a previously unrecognized tumor-suppressive role for ST14: we demonstrate that ST14 overexpression significantly suppresses NSCLC cell proliferation in vitro and tumor growth in vivo. Mechanistically, we identify a novel ST14-Transketolase (TKT) regulatory axis, in which ST14 modulates cellular metabolism through post-translational modifications. Specifically, we establish the following: (i) TKT physically interacts with O-GlcNAc transferase (OGT) to undergo functional O-GlcNAcylation; (ii) ST14 competitively disrupts the TKT-OGT interaction, thereby ablating TKT O-GlcNAcylation; (iii) Such suppression of TKT glycosylation attenuates glycolytic flux, as evidenced by reduced glucose uptake and lactate production; (iv) The resulting metabolic impairment directly inhibits cellular proliferation. Collectively, these findings provide the first mechanistic evidence that ST14 constrains NSCLC cell proliferation via glycosylation-dependent metabolic reprogramming.

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来源期刊
Experimental cell research
Experimental cell research 医学-细胞生物学
CiteScore
7.20
自引率
0.00%
发文量
295
审稿时长
30 days
期刊介绍: Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.
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