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The epigentic dysregulation in pancreatic cancer : from tumor cells to tumor microenviroment

组织者

邬荣领

演讲者

薛婧

时间

2024年11月29日 10:00 至 11:00

地点

A3-4-101

线上

Zoom 388 528 9728 (BIMSA)

摘要

The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) involves a significant accumulation of cancer-associated fibroblasts (CAFs) as part of the host response to tumor cells. The origins and functions of transcriptionally diverse CAF populations in PDAC remain poorly understood. Tumor cell-intrinsic genetic mutations and epigenetic dysregulation may reshape the TME; however, their impacts on CAF heterogeneity remains elusive. SETD2, a histone H3K36 trimethyl-transferase, functions as a tumor suppressor. Through single-cell RNA sequencing, we identify a novel lipid-laden CAF subpopulation marked by ABCA8a in Setd2-deficient pancreatic tumors. Our findings reveal that tumor-intrinsic SETD2 loss unleashes BMP2 signaling via ectopic gain of H3K27Ac, leading to CAFs differentiation towards lipid-rich phenotype. Lipid-laden CAFs then enhance tumor progression by providing lipids for mitochondrial oxidative phosphorylation via ABCA8a transporter. Together, our study links CAF heterogeneity to epigenetic dysregulation in tumor cells, highlighting a previously unappreciated metabolic interaction between CAFs and pancreatic tumor cells.

演讲者介绍

上海交通大学医学院及肿瘤系统医学全国重点实验室研究员，博导，国家优青（肿瘤学，2020年）。近10年来带领团队聚焦胰腺炎症和肿瘤，从表观遗传调控、微环境重塑等方面展开相关病理机制和靶向策略研究。近5年以通讯作者发表研究成果于Cancer Cell，Gut (2024, 2020), Advanced Science（2024，2023）和 Cell Reports 等国际权威杂志20余篇。主持国家自然科学基金 5 项(优青 1 项、面上 3 项、青年 1 项)，上海市东方学者、青年拔尖人才项目。获得华夏青年医学科技奖（2024年）、上海医学科技奖一等奖 (2022年度，第二完成人)、以及美国、国际胰腺协会青年学者奖。现任中华医学会肿瘤学分会青年委员、中国生理学会基质生物学专业委员会委员、以及Cellular oncology副主编、Journal of Pancreatology编委等。