Pathology, research and practice · 2026
ENO2 and BPTF axis drives tumor progression and macrophage polarization in T2DM-associated colorectal cancer.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zhu Zhu, Wang Xueqin, Hu Jia, He Tao, Peng Jibang, Ji Xiang, Liu Chang, Zhou Dayang, Huang Jian
Аннотация
OBJECTIVE: Colorectal cancer (COAD) in the context of type 2 diabetes mellitus (T2DM) is linked with altered immune microenvironment and enhanced tumor progression. In this paper, we clarified enolase 2 (ENO2) as a critical player in T2DM-associated COAD.
METHODS: Using the GSE115313 dataset, we found that ENO2 is significantly upregulated in T2DM-COAD patients and is positively correlated with increased macrophage infiltration and unfavorable outcomes. In a T2DM mouse model, DMH-induced colorectal tumors showed elevated ENO2 expression, enhanced tumor cell proliferation, increased angiogenesis, and a shift in tumor-associated macrophage (TAM) polarization toward the M2 phenotype. ENO2 knockout (KO) mice exhibited reduced tumor formation and TAM infiltration, while ENO2 knock-in (KI) mice displayed more aggressive tumor development.
RESULTS: Mechanistically, ENO2 promotes anaerobic glycolysis in COAD cells, facilitating M2 polarization. BPTF binds to the ENO2 promoter, enhances ENO2 transcription and recruits PHF6 to maintain genomic stability and promote TAM polarization. Inhibition of ENO2 or BPTF in a T2DM-COAD mouse model using specific inhibitors significantly reduced tumor growth, TAM infiltration, and prolonged survival.
CONCLUSION: These findings illustrate that targeting the ENO2-BPTF axis could be a promising strategy for T2DM-associated COAD.
METHODS: Using the GSE115313 dataset, we found that ENO2 is significantly upregulated in T2DM-COAD patients and is positively correlated with increased macrophage infiltration and unfavorable outcomes. In a T2DM mouse model, DMH-induced colorectal tumors showed elevated ENO2 expression, enhanced tumor cell proliferation, increased angiogenesis, and a shift in tumor-associated macrophage (TAM) polarization toward the M2 phenotype. ENO2 knockout (KO) mice exhibited reduced tumor formation and TAM infiltration, while ENO2 knock-in (KI) mice displayed more aggressive tumor development.
RESULTS: Mechanistically, ENO2 promotes anaerobic glycolysis in COAD cells, facilitating M2 polarization. BPTF binds to the ENO2 promoter, enhances ENO2 transcription and recruits PHF6 to maintain genomic stability and promote TAM polarization. Inhibition of ENO2 or BPTF in a T2DM-COAD mouse model using specific inhibitors significantly reduced tumor growth, TAM infiltration, and prolonged survival.
CONCLUSION: These findings illustrate that targeting the ENO2-BPTF axis could be a promising strategy for T2DM-associated COAD.