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High Oestrogen receptor alpha expression correlates with adverse prognosis and promotes metastasis in colorectal cancer

Topi, Geriolda LU ; Satapathy, Shakti Ranjan LU ; Ghatak, Souvik LU ; Hellman, Karin LU ; Ek, Fredrik LU ; Olsson, Roger LU orcid ; Ehrnström, Roy LU ; Lydrup, Marie Louise LU and Sjölander, Anita LU (2024) In Cell Communication and Signaling 22(1).
Abstract

In normal colon tissue, oestrogen receptor alpha (ERα) is expressed at low levels, while oestrogen receptor beta (ERβ) is considered the dominant subtype. However, in colon carcinomas, the ERα/β ratio is often increased, an observation that prompted us to further investigate ERα’s role in colorectal cancer (CRC). Here, we assessed ERα nuclear expression in 351 CRC patients. Among them, 119 exhibited positive ERα nuclear expression, which was significantly higher in cancer tissues than in matched normal tissues. Importantly, patients with positive nuclear ERα expression had a poor prognosis. Furthermore, positive ERα expression correlated with increased levels of the G-protein coupled cysteinyl leukotriene receptor 1 (CysLT1R)... (More)

In normal colon tissue, oestrogen receptor alpha (ERα) is expressed at low levels, while oestrogen receptor beta (ERβ) is considered the dominant subtype. However, in colon carcinomas, the ERα/β ratio is often increased, an observation that prompted us to further investigate ERα’s role in colorectal cancer (CRC). Here, we assessed ERα nuclear expression in 351 CRC patients. Among them, 119 exhibited positive ERα nuclear expression, which was significantly higher in cancer tissues than in matched normal tissues. Importantly, patients with positive nuclear ERα expression had a poor prognosis. Furthermore, positive ERα expression correlated with increased levels of the G-protein coupled cysteinyl leukotriene receptor 1 (CysLT1R) and nuclear β-catenin, both known tumour promoters. In mouse models, ERα expression was decreased in Cysltr1−/− CAC (colitis-associated colon cancer) mice but increased in ApcMin/+ mice with wild-type Cysltr1. In cell experiments, an ERα-specific agonist (PPT) increased cell survival via WNT/β-catenin signalling. ERα activation also promoted metastasis in a zebrafish xenograft model by affecting the tight junction proteins ZO-1 and Occludin. Pharmacological blockade or siRNA silencing of ERα limited cell survival and metastasis while restoring tight junction protein expression. In conclusion, these findings highlight the potential of ERα as a prognostic marker for CRC and its role in metastasis.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
AZD9496, Colorectal cancer, Cysteinyl leukotriene receptors, Metastasis, Oestrogen receptor alpha, PPT, Zebrafish
in
Cell Communication and Signaling
volume
22
issue
1
article number
198
publisher
BioMed Central (BMC)
external identifiers
  • pmid:38549115
  • scopus:85188820131
ISSN
1478-811X
DOI
10.1186/s12964-024-01582-1
language
English
LU publication?
yes
id
923078c9-9067-43a3-827e-94594b58369d
date added to LUP
2024-04-17 15:34:15
date last changed
2024-04-18 03:00:04
@article{923078c9-9067-43a3-827e-94594b58369d,
  abstract     = {{<p>In normal colon tissue, oestrogen receptor alpha (ERα) is expressed at low levels, while oestrogen receptor beta (ERβ) is considered the dominant subtype. However, in colon carcinomas, the ERα/β ratio is often increased, an observation that prompted us to further investigate ERα’s role in colorectal cancer (CRC). Here, we assessed ERα nuclear expression in 351 CRC patients. Among them, 119 exhibited positive ERα nuclear expression, which was significantly higher in cancer tissues than in matched normal tissues. Importantly, patients with positive nuclear ERα expression had a poor prognosis. Furthermore, positive ERα expression correlated with increased levels of the G-protein coupled cysteinyl leukotriene receptor 1 (CysLT<sub>1</sub>R) and nuclear β-catenin, both known tumour promoters. In mouse models, ERα expression was decreased in Cysltr1<sup>−/−</sup> CAC (colitis-associated colon cancer) mice but increased in Apc<sup>Min/+</sup> mice with wild-type Cysltr1. In cell experiments, an ERα-specific agonist (PPT) increased cell survival via WNT/β-catenin signalling. ERα activation also promoted metastasis in a zebrafish xenograft model by affecting the tight junction proteins ZO-1 and Occludin. Pharmacological blockade or siRNA silencing of ERα limited cell survival and metastasis while restoring tight junction protein expression. In conclusion, these findings highlight the potential of ERα as a prognostic marker for CRC and its role in metastasis.</p>}},
  author       = {{Topi, Geriolda and Satapathy, Shakti Ranjan and Ghatak, Souvik and Hellman, Karin and Ek, Fredrik and Olsson, Roger and Ehrnström, Roy and Lydrup, Marie Louise and Sjölander, Anita}},
  issn         = {{1478-811X}},
  keywords     = {{AZD9496; Colorectal cancer; Cysteinyl leukotriene receptors; Metastasis; Oestrogen receptor alpha; PPT; Zebrafish}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Cell Communication and Signaling}},
  title        = {{High Oestrogen receptor alpha expression correlates with adverse prognosis and promotes metastasis in colorectal cancer}},
  url          = {{http://dx.doi.org/10.1186/s12964-024-01582-1}},
  doi          = {{10.1186/s12964-024-01582-1}},
  volume       = {{22}},
  year         = {{2024}},
}