Autophagy induction in tumor surrounding cells promotes tumor growth in adult Drosophila intestines.
Autophagy induction in tumor surrounding cells promotes tumor growth in adult Drosophila intestines.
复制标题
DOI：
10.1016/j.ydbio.2021.04.008
复制
发表时间：
2021-04
影响因子：
2.7
通讯作者：
Hang Zhao;Lin Shi;Ruiyan Kong;Zhengran Li;Fuli Liu;Huiqing Zhao;Zhouhua Li
中科院分区：
文献类型：
--
作者：
Hang Zhao;Lin Shi;Ruiyan Kong;Zhengran Li;Fuli Liu;Huiqing Zhao;Zhouhua Li
在肿瘤发生期间，肿瘤细胞与其周围细胞（微环境）密切相互作用以促进其生长和进展。然而，肿瘤微环境在肿瘤发生和发展中的作用尚未完全了解。在此，我们利用成熟果蝇肠道良性肿瘤模型，发现肿瘤周围的邻近细胞可诱导非细胞自噬（NAA）。通过基因消融肿瘤邻近细胞的自噬诱导可以显著抑制肿瘤生长，表明肿瘤邻近细胞作为肿瘤微环境促进肿瘤生长。肿瘤邻近细胞中的自噬在肿瘤细胞中升高的ROS和激活的JNK信号传导的下游被诱导。有趣的是，我们发现从肿瘤邻近细胞主动转运营养物质（如氨基酸）可维持肿瘤生长，并且增加营养物质的可用性可以显着恢复肿瘤生长。总之，这些数据表明，肿瘤细胞利用其周围的正常相邻细胞作为营养源，通过NAA来满足其生长和进展的高代谢需求。因此，我们提供了深入了解肿瘤细胞及其微环境在肿瘤发展中相互作用的机制。
During tumorigenesis, tumor cells interact intimately with their surrounding cells (microenvironment) for their growth and progression. However, the roles of tumor microenvironment in tumor development and progression are not fully understood. Here, using an established benign tumor model in adultDrosophilaintestines, we find thatnon-cellautonomousautophagy (NAA) is induced in tumor surrounding neighbor cells. Tumor growth can be significantly suppressed by genetic ablation of autophagy induction in tumor neighboring cells, indicating that tumor neighboring cells act as tumor microenvironment to promote tumor growth. Autophagy in tumor neighboring cells is induced downstream of elevated ROS and activated JNK signaling in tumor cells. Interestingly, we find that active transport of nutrients, such as amino acids, from tumor neighboring cells sustains tumor growth, and increasing nutrient availability could significantly restore tumor growth. Together, these data demonstrate that tumor cells take advantage of their surrounding normal neighbor cells as nutrient sources through NAA to meet their high metabolic demand for growth and progression. Thus we provide insights into our understanding of the mechanisms underlying the interaction between tumor cells and their microenvironment in tumor development.