Cancers, Vol. 12, Pages 1772: The ATF6-EGF Pathway Mediates the Awakening of Slow-Cycling Chemoresistant Cells and Tumor Recurrence by Stimulating Tumor Angiogenesis

Cancers, Vol. 12, Pages 1772: The ATF6-EGF Pathway Mediates the Awakening of Slow-Cycling Chemoresistant Cells and Tumor Recurrence by Stimulating Tumor Angiogenesis Cancers doi: 10.3390/cancers12071772 Authors: Jaebeom Cho Hye-Young Min Honglan Pei Xuan Wei Jeong Yeon Sim Shin-Hyung Park Su Jung Hwang Hyo-Jong Lee Sungyoul Hong Young Kee Shin Ho-Young Lee Slow-cycling cancer cells (SCCs) with a quiescence-like phenotype are believed to perpetrate cancer relapse and progression. However, the mechanisms that mediate SCC-derived tumor recurrence are poorly understood. Here, we investigated the mechanisms underlying cancer recurrence after chemotherapy, focusing on the interplay between SCCs and the tumor microenvironment. We established a preclinical model of SCCs by exposing non-small-cell lung cancer (NSCLC) cells to either the proliferation-dependent dye carboxyfluorescein diacetate succinimidyl ester (CFSE) or chemotherapeutic drugs. An RNA sequencing analysis revealed that the established SCCs exhibited the upregulation of a group of genes, especially epidermal growth factor (EGF). Increases in the number of vascular endothelial growth factor receptor (VEGFR)-positive vascular endothelial cells and epidermal growth factor receptor (EGFR) activation were found in NSCLC cell line- and patient-derived xenograft tumors that progressed upon chemotherapy. EGFR tyrosine kinase inhibitors effectively suppressed the migration and tube formation of vascul...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research