课题组人员发现胰岛素样生长因子2（Igf2）是肺神经内分泌干细胞的损伤激活丝裂原，肺神经内分泌干细胞是兼性气道祖细胞，也是小鼠小细胞肺癌的起源细胞。Igf2由干细胞组成，但通过共表达的Igf结合蛋白（Igfbps）被隔离在生态位中。气道损伤释放Igf2，通过短暂激活Igf2受体和抑制视网膜母细胞瘤（Rb）肿瘤抑制因子诱导细胞增殖。Rb缺失激活永久通路，启动持续干细胞分裂。除了它们在生理、生长和衰老中的经典激素作用外，Igf蛋白还与Igfbp和Rb一起局部快速地起作用，控制损伤诱导的干细胞增殖和肿瘤发生。
据介绍，干细胞在损伤后增殖修复受损组织，慢性损伤可促进癌症。然而，损伤激活信号和调控机制以及它们与癌症的关系尚不清楚。
附：英文原文
Title: Stem cell control in the lung by an autocrine injury-activated Igf complex
Author: Yue Zhang, Youcef Ouadah, Yin Liu, Maya E. Kumar, Makenna M. Morck, Mark A. Krasnow
Issue&Volume: 2026-04-16
Abstract: Stem cells proliferate after injury to repair damaged tissue, and chronic injury can promote cancer. However, the injury-activated signals and regulatory mechanisms, and their relationship to cancer, are poorly understood. Here, we identified insulin-like growth factor 2 (Igf2) as an injury-activated mitogen for lung neuroendocrine stem cells, which are facultative airway progenitors and a cell of origin of small-cell lung cancer in mice. Igf2 was constitutively produced by the stem cells but sequestered in the niche by coexpressed Igf binding proteins (Igfbps). Airway injury released Igf2 and induced proliferation by transiently activating Igf2 receptors and repressing retinoblastoma (Rb) tumor suppressor. Permanent pathway activation by Rb deletion initiated continuous stem cell division. Thus, beyond their classical hormonal roles in physiology, growth, and aging, Igf proteins operate locally and rapidly with Igfbp and Rb to control injury-induced stem cell proliferation and tumor initiation.
DOI: adt1310
Source: https://www.science.org/doi/10.1126/science.adt1310