Interplay between Signaling Pathways and Tumor Microenvironment Components: A Paradoxical Role in Colorectal Cancer

Int J Mol Sci. 2023 Mar 15;24(6):5600. doi: 10.3390/ijms24065600.

Abstract

The study of the tumor microenvironment (TME) has become an important part of colorectal cancer (CRC) research. Indeed, it is now accepted that the invasive character of a primary CRC is determined not only by the genotype of the tumor cells, but also by their interactions with the extracellular environment, which thereby orchestrates the development of the tumor. In fact, the TME cells are a double-edged sword as they play both pro- and anti-tumor roles. The interaction of the tumor-infiltrating cells (TIC) with the cancer cells induces the polarization of the TIC, exhibiting an antagonist phenotype. This polarization is controlled by a plethora of interconnected pro- and anti-oncogenic signaling pathways. The complexity of this interaction and the dual function of these different actors contribute to the failure of CRC control. Thus, a better understanding of such mechanisms is of great interest and provides new opportunities for the development of personalized and efficient therapies for CRC. In this review, we summarize the signaling pathways linked to CRC and their implication in the development or inhibition of the tumor initiation and progression. In the second part, we enlist the major components of the TME and discuss the complexity of their cells functions.

Keywords: colorectal cancer; dual function; effectors; signaling pathways; tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Cell Transformation, Neoplastic
  • Colorectal Neoplasms* / pathology
  • Humans
  • Signal Transduction
  • Tumor Microenvironment

Grants and funding

This work was supported by the Tunisian Ministry of Higher Education and Research (LR16IPT04). The funders had no role in the decision to publish or in the preparation of the manuscript.