Tumor Microenvironment Remodeling in Gastrointestinal Cancer: Role of miRNAs as Biomarkers of Tumor Invasion

Abstract

Gastrointestinal (GI) cancers are the most frequent neoplasm, responsible for half of all cancer-related deaths. Metastasis is the leading cause of death from GI cancer; thus, studying the processes that regulate cancer cell migration is of paramount importance for the development of new therapeutic strategies. In this review, we summarize the mechanisms adopted by cancer cells to promote cell migration and the subsequent metastasis formation by highlighting the key role that tumor microenvironment components play in deregulating cellular pathways involved in these processes. We, therefore, provide an overview of the role of different microRNAs in promoting tumor metastasis and their role as potential biomarkers for the prognosis, monitoring, and diagnosis of GI cancer patients. Finally, we relate the possible use of nutraceuticals as a new strategy for targeting numerous microRNAs and different pathways involved in GI tumor invasiveness.

Keywords: EMT; biomarker; gastrointestinal tumors; metastasis; miRNA; nutraceuticals; tumor cell migration; tumor microenvironment.

Figure 1

Schematic representation of gastrointestinal TME and biological events leading to cell migration and metastasis formation. A pro-tumoral environment is established in the TME of GI tumors given by the presence of activated CAFs and immunosuppressive immune cells, leading to the production of cytokines, chemokines, and soluble factors. These are responsible for ECM remodeling and promotion of EMT that enhances tumor cell motility and subsequent metastasis formation. The figure was created with BioRender.com.