Evidence mapPaperPMID 41701476Full record

ArticleClinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2026

S100A10 promotes glycolysis and malignant progression of CCA by activating the HK2/ERK signaling pathway.

Yajun Wang, Wenjie Chen, Wei Liu, Xu Zhang, Yongxing Wang, Niu Dai

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Article in Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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6 authors.

Yajun Wang *Department of General Surgery, The 969th, Hospital of the Joint Logistics Support Force of People's Liberation Army, Hohhot, 010051, China.
Wenjie Chen *Department of Hematology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Wei Liu *Department of General Surgery, The 969th, Hospital of the Joint Logistics Support Force of People's Liberation Army, Hohhot, 010051, China.
Xu ZhangDepartment of General Surgery, The 969th, Hospital of the Joint Logistics Support Force of People's Liberation Army, Hohhot, 010051, China. zhangxu291@163.com.
Yongxing WangDepartment of General Surgery, The 969th, Hospital of the Joint Logistics Support Force of People's Liberation Army, Hohhot, 010051, China. wyx4787@163.com.
Niu DaiDepartment of General Surgery, The 969th, Hospital of the Joint Logistics Support Force of People's Liberation Army, Hohhot, 010051, China. dainiu1016@163.com.ORCID http://orcid.org/0009-0007-6326-0562

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6 · The paper itself

Abstract

BACKGROUND &

aimsCholangiocarcinoma (CCA) is a highly aggressive malignancy characterized by late diagnosis and poor prognosis. The molecular mechanisms driving CCA progression and metabolic reprogramming remain incompletely understood. This study aimed to elucidate the clinical significance, biological function, and underlying mechanisms of the calcium-binding protein S100A10 in CCA pathogenesis.

methodsS100A10 expression was analyzed using TCGA and Human Protein Atlas datasets and validated in a clinical cohort of 46 CCA patients. The diagnostic value and prognostic associations were evaluated statistically. Loss-of-function assays (shRNA knockdown) were performed in HuCCT1 cells to assess proliferation, migration, invasion, and apoptosis. Mechanistic investigations involved metabolic assays (glucose uptake/lactate release), Western blotting, and rescue experiments targeting the Hexokinase 2 (HK2) and ERK signaling pathways.

resultsBioinformatic analysis and clinical validation revealed that S100A10 is significantly upregulated in CCA tissues compared to normal controls, with a high diagnostic accuracy (AUC = 0.917). Elevated S100A10 expression correlated significantly with advanced tumor stage and shortened overall survival. Functionally, S100A10 silencing markedly attenuated CCA cell proliferation, migration, and invasion while promoting apoptosis. Mechanistically, S100A10 was found to orchestrate metabolic reprogramming by enhancing aerobic glycolysis. This effect was mediated through the regulation of key glycolytic enzymes, particularly HK2, and the activation of the ERK signaling cascade. Notably, the suppression of malignant phenotypes induced by S100A10 depletion was partially reversed by either HK2 overexpression or pharmacological ERK activation.

conclusionsThis study identifies S100A10 as a critical oncogenic driver in CCA that links metabolic reprogramming to tumor progression via the HK2/ERK signaling axis. These findings suggest S100A10 is a robust prognostic biomarker and a potential therapeutic target for disrupting the metabolic adaptability of cholangiocarcinoma.

Indexed as

Bile Duct NeoplasmsCholangiocarcinomaGlycolysisHexokinaseMAP Kinase Signaling SystemS100 ProteinsApoptosisCell Line, TumorCell MovementCell ProliferationDisease ProgressionFemaleHumansMaleMetabolic ReprogrammingMiddle AgedHexokinaseHK2 protein, humanS100 Calcium Binding Protein A10S100 ProteinsCCAERK signalling pathwayGlycolysisHK2S100A10

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.