近日，美国纪念斯隆-凯特琳癌症中心Scott W. Lowe及其团队的论文发现了在从良性向恶性转变的过程中，致癌力量与抑癌力量共同汇聚于一个祖细胞微环境。相关论文于2026年4月15日发表于国际顶尖学术期刊《细胞》杂志上。
为了研究恶性肿瘤何时以及如何发生以及组织重组进行，课题组在胰腺导管腺癌（PDAC）的小鼠模型中结合单细胞和空间转录组学分析，捕获了p53的自发丢失。在Kras突变细胞中，该课题组研究人员发现致癌和肿瘤抑制程序，包括那些由p53、CDKN2A和SMAD4控制的程序，在一个离散的祖细胞样群体中被共同激活，参与衰老样反应。使用该课题组研究人员开发的空间分析框架，该课题组研究人员发现以这些细胞为中心的生态位在肿瘤进展过程中经历了逐步重塑，反映了侵袭性PDAC。短暂的KRAS抑制耗尽祖细胞样细胞并拆除其生态位，延迟恶性肿瘤的开始。相反，p53抑制使祖细胞扩增、上皮-间质重编程和免疫特权生态位形成。这些发现将祖细胞样状态定位于癌症驱动突变、可塑性和组织重塑的交汇处，揭示了阻断恶性肿瘤的关键窗口。
研究人员表示，良性到恶性的转变是癌症发展的决定性步骤。
附：英文原文
Title: Oncogenic and tumor-suppressive forces converge on a progenitor niche at the benign-to-malignant transition
Author: José Reyes, Isabella Del Priore, Andrea C. Chaikovsky, Nikhita Pasnuri, Ahmed M. Elhossiny, Jin Park, Philipp Weiler, Tobias Krause, Andrew Moorman, Catherine Snopkowski, Meril Takizawa, Cassandra Burdziak, Nalin Ratnayeke, Ignas Masilionis, Yu-Jui Ho, Ronan Chaligné, Paul B. Romesser, Aveline Filliol, Tal Nawy, John P. Morris, Zhen Zhao, Marina Pasca Di Magliano, Direna Alonso-Curbelo, Dana Pe’er, Scott W. Lowe
Issue&Volume: 2026-04-15
Abstract: The benign-to-malignant transition is a defining step in cancer progression. To investigate when and how malignancy initiation occurs and tissue reorganization proceeds, we combine single-cell and spatial transcriptomic profiling in mouse models of pancreatic ductal adenocarcinoma (PDAC) that capture spontaneous p53 loss. Among Kras-mutant cells, we find that oncogenic and tumor-suppressive programs, including those controlled by p53, CDKN2A, and SMAD4, are co-activated in a discrete progenitor-like population, engaging senescence-like responses. Using a framework we developed for spatial analysis, we show that a niche centered on these cells undergoes stepwise remodeling during tumor progression, mirroring invasive PDAC. Transient KRAS inhibition depletes progenitor-like cells and dismantles their niche, delaying malignancy initiation. Conversely, p53 suppression enables progenitor cell expansion, epithelial-mesenchymal reprogramming, and immune-privileged niche formation. These findings position the progenitor-like state at the convergence of cancer-driving mutations, plasticity, and tissue remodeling, revealing a critical window for intercepting malignancy.
DOI: 10.1016/j.cell.2026.03.032
Source: https://www.cell.com/cell/abstract/S0092-8674(26)00333-8