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

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.

Advances in Precision Medicine Approaches for Colorectal Cancer: From Molecular Profiling to Targeted Therapies

“…Tumors with a robust immune response tend to exhibit slower growth and a lower risk of metastasis. Consequently, the assessment of TIL levels in colorectal tumors has emerged as a promising prognostic biomarker, helping clinicians predict patient outcomes and inform treatment decisions. , …”

“…Consequently, the assessment of TIL levels in colorectal tumors has emerged as a promising prognostic biomarker, helping clinicians predict patient outcomes and inform treatment decisions. 124,125 Furthermore, the role of the stromal component within the tumor microenvironment is increasingly recognized. Cancerassociated fibroblasts (CAFs) are a major component of the stroma and play a crucial role in promoting tumor growth and invasion.…”

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

“…Additionally, in CRC, crosstalk between TME and tumor cells plays a key role in invasiveness, metastasis formation, and drug resistance. TME regulates a plethora of cellular signaling pathways that control multiple stages of tumor progression and invasion, such as mitogen-activated protein kinase (MAPKs), PI3K/Akt, NF-κB, JAK/STAT, Wnt/β-catenin, TGF-β, and Notch [ 38 ].…”

Multi-dataset study on neoadjuvant treatment-related prognostic model and molecular network mechanism of locally advanced rectal cancer

“…TME is a miniature ecosystem created by tumor cells, which consists of tumor cells, mesenchymal cells, and other components. Different components in the tumor microenvironment all play different roles in tumor development, and the dynamic interactions between tumor cells and their surrounding cellular and non-cellular components are closely related to tumor-generated heterogeneity, clonal evolution, and drug resistance formation [11][12][13][14]. The tumor microenvironment in LARC exhibits signi cant heterogeneity in the presence of immune cells.…”