High Oestrogen receptor alpha expression correlates with adverse prognosis and promotes metastasis in colorectal cancer
(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
- Topi, Geriolda LU ; Satapathy, Shakti Ranjan LU ; Ghatak, Souvik LU ; Hellman, Karin LU ; Ek, Fredrik LU ; Olsson, Roger LU ; Ehrnström, Roy LU ; Lydrup, Marie Louise LU and Sjölander, Anita LU
- organization
-
- LUCC: Lund University Cancer Centre
- Cell Pathology, Malmö (research group)
- MultiPark: Multidisciplinary research focused on Parkinson´s disease
- Chemical Biology and Therapeutics (research group)
- LU Profile Area: Light and Materials
- LTH Profile Area: Nanoscience and Semiconductor Technology
- NanoLund: Centre for Nanoscience
- Centre for Analysis and Synthesis
- publishing date
- 2024-12
- 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}}, }