dc.contributor.author |
Azubuike, Udochi Felicia
|
|
dc.contributor.author |
Newton, Claire L.
|
|
dc.contributor.author |
Van den Bout, Iman
|
|
dc.date.accessioned |
2022-12-14T05:43:03Z |
|
dc.date.available |
2022-12-14T05:43:03Z |
|
dc.date.issued |
2022-08-06 |
|
dc.description |
DATA AVAILABILITY STATEMENT : All data recorded in this study is archived online within Benchling.com
and is available upon request to the corresponding author. |
en_US |
dc.description.abstract |
Kisspeptin is an anti-metastatic mediator in many cancer types, acting through its receptor,
KISS1R. However, controversy remains regarding its role in breast cancer since both pro- and antimetastatic roles have been ascribed to it. In KISS1R overexpressing triple-negative breast cancer
(TNBC) cells, stimulation has been associated with increased invasion and MMP-9 expression, leading
to the suggestion that hormone receptor status determines the metastatic effects of kisspeptin. To
assess the veracity of this claim, we compared endogenous KISS1R signalling and physiological
output in the hormone receptor-negative MDA-MB-231 and BT-20 cell lines after KP-10 (shortest
active kisspeptin peptide) stimulation. MDA-MB-231 cells are metastatic when implanted in mice
while BT-20 are not and remain epithelial-like. We show that both cell lines express KISS1R mRNA
and respond to KP-10 by elevating calcium mobilisation. However, KP-10 stimulation induced
migration of MDA-MB-231, but not BT-20 cells, in a calcium-dependent manner. Moreover, only
BT-20 cells responded to KP-10 by increasing ERK phosphorylation in a β-arrestin-dependent manner.
Interestingly, both cell lines displayed different complements of β-arrestin 1 and 2 expression. Overall,
our data shows that, in TNBC, it is not universally true that kisspeptin/KISS1R stimulate migration
or pro-metastatic behaviour, as divergent responses were observed in the two TNBC lines tested.
Whether this divergence is related to the observed differences in β-arrestin complements warrants
further investigation and may enable further stratification of the ability of kisspeptin to influence
breast tumour behaviour. |
en_US |
dc.description.department |
Immunology |
en_US |
dc.description.department |
Physiology |
en_US |
dc.description.sponsorship |
The National Research Foundation, South Africa and SGKN Trust. |
en_US |
dc.description.uri |
https://www.mdpi.com/journal/ijerph |
en_US |
dc.identifier.citation |
Azubuike, U.F.; Newton,
C.L.; van den Bout, I. Lack of
Oestrogen Receptor Expression in
Breast Cancer Cells Does Not
Correlate with Kisspeptin Signalling
and Migration. International Journal of Molecular Sciences. 2022,
23, 8744. https://doi.org/10.3390/ijms23158744. |
en_US |
dc.identifier.issn |
1422-0067 (online) |
|
dc.identifier.issn |
1661-6596 (print) |
|
dc.identifier.other |
10.3390/ijms23158744 |
|
dc.identifier.uri |
https://repository.up.ac.za/handle/2263/88782 |
|
dc.language.iso |
en |
en_US |
dc.publisher |
MDPI |
en_US |
dc.rights |
© 2022 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/). |
en_US |
dc.subject |
KISS1R |
en_US |
dc.subject |
Metastasis |
en_US |
dc.subject |
Breast cancer |
en_US |
dc.subject |
Oestrogen receptor |
en_US |
dc.subject |
Calcium signalling |
en_US |
dc.subject |
Extracellular regulated kinase (ERK) |
en_US |
dc.subject |
Cell migration |
en_US |
dc.subject |
Kisspeptin |
en_US |
dc.title |
Lack of oestrogen receptor expression in breast cancer cells does not correlate with kisspeptin signalling and migration |
en_US |
dc.type |
Article |
en_US |