PO.TB02.02 · 肿瘤生物学
发现一种进化上保守的GPCR样蛋白，其塑造胶质母细胞瘤细胞网络
Discovery of an evolutionarily conserved GPCR-like protein shaping glioblastoma cell networks
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摘要 Abstract
中文摘要
多形性胶质母细胞瘤（GBM）是最具侵袭性和致死性的脑癌之一，尽管在外科手术、放疗和化疗方面取得了进展，中位生存期仍约为20个月。GBM的一个决定性形态学特征是肿瘤微管（TMs）的形成，即在肿瘤细胞之间建立开放式通道的细长胞质延伸结构。这些结构将孤立的GBM细胞转变为一个协调的多细胞网络，能够在远距离间快速转运胞质成分，重塑肿瘤行为并促进治疗抵抗。利用AI驱动的结构学方法，我们实验室鉴定出TM184C，这是一种古老的GPCR样蛋白，可调控自噬以及细胞间连接的形成和跨细胞的物质与细胞器转运。值得注意的是，过表达TM184C的HEK293A细胞可产生细胞间连接，这些连接在表型上重现了在患者来源的GBM细胞中观察到的TM184C阳性结构和囊泡分布。鉴于这些发现，以及TM184C表达与GBM不良预后相关的观察结果，我们将报告我们在阐明TM184C如何促进GBM突起、细胞间连接和肿瘤进展方面所做的工作。
查看英文原文 English abstract
Glioblastoma multiforme (GBM) is among the most aggressive and lethal brain cancers, and despite advances in surgery, radiation, and chemotherapy, median survival remains approximately 20 months. A defining morphological feature of GBM is the formation of tumor microtubules (TMs), thin cytoplasmic extensions that create open-ended channels between tumor cells. These structures transform isolated GBM cells into a coordinated multicellular network capable of rapidly transferring cytoplasmic components across distance, reshaping tumor behavior and promoting therapy resistance. Using AI-driven structural approaches, our lab identified TM184C, an ancient GPCR-like protein that regulates autophagy and the formation of intercellular connections and transcellular material and organelle transfer. Notably, HEK293A cells overexpressing TM184C generate intercellular connections that phenocopy the TM184C-positive structures and vesicle distributions observed in patient-derived GBM cells. Given these findings, and the observation that TM184C expression correlates with poor prognosis in GBM, we will report on our efforts to define how TM184C contributes to GBM projections, intercellular connectivity, and tumor progression.
利益披露 Disclosure
J. Arcuri, None..
B. Colon, None.