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Elucidating the Association Between the Upregulation of Angiotensin Type 1-Receptors and the Development of Gastrointestinal Malignancies

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Abstract

The renin-angiotensin system (RAS) is a major regulator of body fluid hemostasis and blood pressure. Angiotensin type 1 receptors (AT1R) are one of the major components of this system and are widely expressed in different organs, including the gastrointestinal (GI) system. Very little known about the physiological roles of AT1R in GI tract but evidence has reported that local AT1Rs are upregulated in pathological conditions like GI malignancies and play role in stimulation of signaling pathways associated with GI cancers progression. AT1Rs axes signaling in tumor microenvironments stimulate inflammation and facilitate vascularization around the tumor cell to display invasive behavior. AT1Rs in stroma cells promote tumor-associated angiogenesis by upregulated of vessel endothelial growth factor (VEGF). Also, AT1Rs by the activation of molecular mechanisms such as PI3/Akt/NF-κB pathways increase the invasion of tumor cells. Experimental and clinical studies have reported that AT1R antagonists have beneficial influences by increasing the survival of patients with GI malignancies and reduction in the proliferation of GI cancer cell lines in vitro, and the growth and metastasis of tumors in vivo, therefore, AT1Rs antagonist have the potential for future anticancer strategies. This review focuses on the pathological roles of AT1Rs in GI malignancies.

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Abbreviations

AngII:

Angiotensin II

RAS:

Renin angiotensin system

AT1R:

Angiotensin type 1 receptor

ACE:

Angiotensin convert enzyme

COX-2:

Cyclooxygenase-2

EGFR:

Epithermal growth factor receptor

FGF:

Fibroblast growth factor

GI:

Gastrointestinal

HIF1α:

hypoxia inducible factor 1α

MAPK:

Mitogen activation protein kinase

NF-kB:

Nuclear factor kappa B

PKC:

Protein kinase C

TAMs:

Tumor-associated macrophages

PDGF:

Platelet-derived growth factor

PKB:

Protein kinase B

PPARγ:

Peroxisome proliferator–activated receptor γ

VEGF:

Vessel endothelial growth factor

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  1. Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran

    Mohammad-Hassan Arjmand

  2. Cancer Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran

    Mohammad-Hassan Arjmand

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Arjmand, MH. Elucidating the Association Between the Upregulation of Angiotensin Type 1-Receptors and the Development of Gastrointestinal Malignancies. J Gastrointest Canc 52, 399–406 (2021). https://doi.org/10.1007/s12029-020-00547-0

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