Hypoxic Exosomal circPLEKHM1-Mediated Crosstalk between Tumor Cells and Macrophages Drives Lung Cancer Metastasis
Hypoxic Exosomal circPLEKHM1-Mediated Crosstalk between Tumor Cells and Macrophages Drives Lung Cancer Metastasis | |
Author | Wang, DL; Wang, S; Jin, MM; Zuo, Y; Wang, JP; Niu, Y; Zhou, Q; Chen, JW; Tang, XR; Tang, WX; Liu, XY; Yu, H; Yan, WJ; Wei, HH; Huang, G; Song, SL; Tang, S |
Journal | ADVANCED SCIENCE |
Pub Year | 2024 |
Type | |
Abstract | Intercellular communication often relies on exosomes as messengers and is critical for cancer metastasis in hypoxic tumor microenvironment. Some circular RNAs (circRNAs) are enriched in cancer cell-derived exosomes, but little is known about their ability to regulate intercellular communication and cancer metastasis. Here, by systematically analyzing exosomes secreted by non-small cell lung cancer (NSCLC) cells, a hypoxia-induced exosomal circPLEKHM1 is identified that drives NSCLC metastasis through polarizing macrophages toward to M2 type. Mechanistically, exosomal circPLEKHM1 promoted PABPC1-eIF4G interaction to facilitate the translation of the oncostatin M receptor (OSMR), thereby promoting macrophage polarization for cancer metastasis. Importantly, circPLEKHM1-targeted therapy significantly reduces NSCLC metastasis in vivo. circPLEKHM1 serves as a prognostic biomarker for metastasis and poor survival in NSCLC patients. This study unveils a new circRNA-mediated mechanism underlying how cancer cells crosstalk with macrophages within the hypoxic tumor microenvironment to promote metastasis, highlighting the importance of exosomal circPLEKHM1 as a prognostic biomarker and therapeutic target for lung cancer metastasis. A hypoxia-induced exosomal circRNA, circPLEKHM1, drives lung cancer metastasis by educating macrophages in the tumor microenvironment. circPLEKHM1 functions as a scaffold for PABPC1-eIF4G interaction to facilitate the translation of the oncostatin M receptor, polarizing macrophages towards to M2 type for cancer metastasis. circPLEKHM1 is a significant prognostic biomarker and effective therapeutic target for M2 macrophage-involved cancer metastasis. image |
SCI | 14.3 |