Fig. 8

Schematic representation of the miR-548k proposed mode of action in modulating ESCC tumor responses. miR-548k functions as an oncogene in ESCC cells by directly dampening KLF10, a transcriptional repressor of EGFR, thus leading to transcriptional activation of EGFR and subsequently activation of its downstream effectors ERK and Akt, which promote cell proliferation, migration and invasion. In addition, miR-548k functions as a mediator of intercellular communication within the tumor microenvironment by targeting ADAMTS1, resulting in more amount of VEGFC releasing from ADAMTS1 sequestration. Secretory VEGFC stimulates VEGFR3 activation in infiltrated dermal lymphatic endothelial cells and leads to lymphangiogensis and promotes lymphatic metastasis