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
Abstract
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.
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.