EMT Mechanism, Lung Cancer Metastasis, and microRNA

Cancer metastasis occurs due to several causes such as histologic, genetic, and pathologic features. Hematogenous spread, lymphatic spread, and direct spread to pleura are the main routes of lung metastasis (Stella et al., 2019). The primary sites of the tumor may affect the route of the spread. Many interesting theories exist regarding the origin of metastatic cells. Jamil and Kasi summarized that there would be main roots for the lung metastasis among these theories: 1). epithelial-mesenchymal transition (EMT) in which epithelial stem cells transform into mesenchymal cells, 2). stem cell origin of metastatic tumors in which tissue stem cells are the origin of metastatic cancers, 3). a concept of macrophage facilitation of metastasis in which tumor-associated macrophages contribute to tumor progression, and 4). myeloid cell origin of metastasis in which myeloid origin cells with mesenchymal properties promotes metastasis (Jamil and Kasi, 2021). The signaling pathways involved in the microenvironment include Rous sarcoma virus tyrosine kinase signaling and p38 and extracellular signal-related kinase-1 (ERK) mitogen-activated protein kinase (MAPK) signaling. Adhesion and extracellular matrix molecules are also important to establish metastatic mass.