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

Stefani, Constantin; Miricescu, Daniela; Stanescu-Spinu, Iulia-Ioana; Nica, Remus Iulian; Greabu, Maria; Totan, Alexandra Ripszky; Jinga, Mariana

doi:10.3390/ijms221910260

Open AccessReview

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

by

Constantin Stefani

¹,

Daniela Miricescu

^2,*,

Iulia-Ioana Stanescu-Spinu

²,

Remus Iulian Nica

³,

Maria Greabu

^2,*,

Alexandra Ripszky Totan

²

and

Mariana Jinga

⁴

¹

Department of Family Medicine and Clinical Base, ‘‘Dr. Carol Davila’ Central Military Emergency University Hospital, 051075 Bucharest, Romania

²

Department of Biochemistry, Faculty of Dental Medicine, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd, 050474 Bucharest, Romania

³

Surgery 2, ‘Dr. Carol Davila’ Central Military Emergency University Hospital, 051075 Bucharest, Romania

⁴

Department of Gastroenterology, ‘Dr. Carol Davila’ Central Military Emergency University Hospital, 051075 Bucharest, Romania

^*

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2021, 22(19), 10260; https://doi.org/10.3390/ijms221910260

Submission received: 12 August 2021 / Revised: 19 September 2021 / Accepted: 20 September 2021 / Published: 23 September 2021

(This article belongs to the Special Issue Oncogenic Signaling of Growth Factor Receptors in Cancer: Mechanisms and Therapeutic Opportunities)

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

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MDPI and ACS Style

Stefani, C.; Miricescu, D.; Stanescu-Spinu, I.-I.; Nica, R.I.; Greabu, M.; Totan, A.R.; Jinga, M. Growth Factors, PI3K/AKT/mTOR and MAPK Signaling Pathways in Colorectal Cancer Pathogenesis: Where Are We Now? Int. J. Mol. Sci. 2021, 22, 10260. https://doi.org/10.3390/ijms221910260

AMA Style

Stefani C, Miricescu D, Stanescu-Spinu I-I, Nica RI, Greabu M, Totan AR, Jinga M. Growth Factors, PI3K/AKT/mTOR and MAPK Signaling Pathways in Colorectal Cancer Pathogenesis: Where Are We Now? International Journal of Molecular Sciences. 2021; 22(19):10260. https://doi.org/10.3390/ijms221910260

Chicago/Turabian Style

Stefani, Constantin, Daniela Miricescu, Iulia-Ioana Stanescu-Spinu, Remus Iulian Nica, Maria Greabu, Alexandra Ripszky Totan, and Mariana Jinga. 2021. "Growth Factors, PI3K/AKT/mTOR and MAPK Signaling Pathways in Colorectal Cancer Pathogenesis: Where Are We Now?" International Journal of Molecular Sciences 22, no. 19: 10260. https://doi.org/10.3390/ijms221910260

APA Style

Stefani, C., Miricescu, D., Stanescu-Spinu, I.-I., Nica, R. I., Greabu, M., Totan, A. R., & Jinga, M. (2021). Growth Factors, PI3K/AKT/mTOR and MAPK Signaling Pathways in Colorectal Cancer Pathogenesis: Where Are We Now? International Journal of Molecular Sciences, 22(19), 10260. https://doi.org/10.3390/ijms221910260

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

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