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Review
. 2021 Sep 23;22(19):10260.
doi: 10.3390/ijms221910260.

Growth Factors, PI3K/AKT/mTOR and MAPK Signaling Pathways in Colorectal Cancer Pathogenesis: Where Are We Now?

Constantin Stefani  1 , Daniela Miricescu  2 , Iulia-Ioana Stanescu-Spinu  2 , Remus Iulian Nica  3 , Maria Greabu  2 , Alexandra Ripszky Totan  2 , Mariana Jinga  4
Affiliations
Review

Growth Factors, PI3K/AKT/mTOR and MAPK Signaling Pathways in Colorectal Cancer Pathogenesis: Where Are We Now?

Constantin Stefani et al. Int J Mol Sci. .

Abstract

Colorectal cancer (CRC) is a predominant malignancy worldwide, being the fourth most common cause of mortality and morbidity. The CRC incidence in adolescents, young adults, and adult populations is increasing every year. In the pathogenesis of CRC, various factors are involved including diet, sedentary life, smoking, excessive alcohol consumption, obesity, gut microbiota, diabetes, and genetic mutations. The CRC tumor microenvironment (TME) involves the complex cooperation between tumoral cells with stroma, immune, and endothelial cells. Cytokines and several growth factors (GFs) will sustain CRC cell proliferation, survival, motility, and invasion. Epidermal growth factor receptor (EGFR), Insulin-like growth factor -1 receptor (IGF-1R), and Vascular Endothelial Growth Factor -A (VEGF-A) are overexpressed in various human cancers including CRC. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) and all the three major subfamilies of the mitogen-activated protein kinase (MAPK) signaling pathways may be activated by GFs and will further play key roles in CRC development. The main aim of this review is to present the CRC incidence, risk factors, pathogenesis, and the impact of GFs during its development. Moreover, the article describes the relationship between EGF, IGF, VEGF, GFs inhibitors, PI3K/AKT/mTOR-MAPK signaling pathways, and CRC.

Keywords: MAPK; PI3K/AKT/mTOR; colorectal cancer; growth factor inhibitors; growth factors.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The environmental and genetic factors involved in colorectal cancer progression.
Figure 2
Figure 2
Growth factors, growth factor inhibitors, and PI3K/AKT/mTOR-MAPK signaling pathways in colorectal cancer development.
See this image and copyright information in PMC

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