Kinin Receptors B1 and B2 Mediate Breast Cancer Cell Migration and Invasion by Activating the FAK-Src Axis

Journal
International Journal of Molecular Sciences
ISSN
1422-0067
Date Issued
2024
Author(s)
Felipe González-Turén
Lorena Lobos-González
Alexander Riquelme-Herrera
Andrés Ibacache
Luis Meza Ulloa
Alexandra Droguett
Camila Alveal
Bastián Carrillo
Javiera Gutiérrez
Pamela Ehrenfeld
Areli Cárdenas-Oyarzo
Type
journal-article
DOI
URL
Abstract
Kinin receptors B1 and B2 are involved in migration and invasion in gastric, glioma, and cervical cancer cells, among others. However, the role of kinin receptors in breast cancer cells has been poorly studied. We aimed to reveal the impact of B1 and B2 receptors on migration and invasion in breast cancer cells and demonstrate their capacity to modulate in vivo tumor growth. MDA-MB-231, MCF-7, and T47D cells treated with Lys-des[Arg9]bradykinin (LDBK) or bradykinin (BK) were used to evaluate migration and invasion. Des-[Arg9]-Leu8-BK and HOE-140 were used as antagonists for the B1 and B2 receptors. MDA-MB-231 cells incubated or not with antagonists were subcutaneously inoculated in BALBc NOD/SCID mice to evaluate tumor growth. LDBK and BK treatment significantly increased migration and invasion in breast cancer cells, effects that were negated when antagonists were used. The use of antagonists in vivo inhibited tumor growth. Moreover, the migration and invasion induced by kinins in breast cancer cells were inhibited when focal adhesion kinase (FAK) and Src inhibitors were used. The novelty revealed in our work is that B1 and B2 receptors activated by LDBK and BK induce migration and invasion in breast cancer cells via a mechanism that involves the FAK–Src signaling pathway, and the antagonism of both receptors in vivo impairs breast tumor growth.
Project(s)
Subjects
b1 receptor

; 

b2 receptor

; 

breast cancer

; 

fak

; 

invasion

; 

kinin receptors

; 

migration

; 

src

; 

animals

; 

bradykinin

; 

breast neoplasms

; 

cell line, tumor

; 

cell movement

; 

cell proliferation

; 

female

; 

focal adhesion kinase 1

; 

focal adhesion protein-tyrosine kinases

; 

humans

; 

mcf-7 cells

; 

mice

; 

mice, inbred balb c

; 

mice, inbred nod

; 

mice, scid

; 

neoplasm invasiveness

; 

receptor, bradykinin b1

; 

receptor, bradykinin b2

; 

signal transduction

; 

src-family kinases

; 

bradykinin b1 receptor

; 

bradykinin b1 receptor antagonist

; 

bradykinin b2 receptor

; 

bradykinin b2 receptor antagonist

; 

focal adhesion kinase

; 

focal adhesion kinase inhibitor

; 

mitomycin

; 

bradykinin

; 

bradykinin b1 receptor

; 

bradykinin b2 receptor

; 

focal adhesion kinase

; 

focal adhesion kinase 1

; 

protein tyrosine kinase

; 

ptk2 protein, human

; 

animal experiment

; 

animal model

; 

article

; 

breast cancer

; 

breast cancer cell line

; 

cancer growth

; 

cancer inhibition

; 

cell invasion

; 

cell migration

; 

cell viability

; 

controlled study

; 

enzyme activation

; 

female

; 

human

; 

human cell

; 

in vivo study

; 

mcf-7 cell line

; 

mda-mb-231 cell line

; 

mouse

; 

nod scid mouse

; 

nonhuman

; 

t-47d cell line

; 

transwell assay

; 

wound closure

; 

animal

; 

bagg albino mouse

; 

breast tumor

; 

cell motion

; 

cell proliferation

; 

drug effect

; 

metabolism

; 

nonobese diabetic mouse

; 

pathology

; 

scid mouse

; 

signal transduction

; 

tumor cell line

; 

tumor invasion