Endocrine Resistance in Breast Cancer: The Role of Estrogen Receptor Stability
Therapy of hormone receptor positive breast cancer (BCa) generally targets estrogen receptor (ER) function and signaling by reducing estrogen production or by blocking its interaction with the ER. Despite good long-term responses, resistance to treatment remains a significant issue, with approximate...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-09-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/9/9/2077 |
| _version_ | 1797553993156657152 |
|---|---|
| author | Sarah A. Jeffreys Branka Powter Bavanthi Balakrishnar Kelly Mok Patsy Soon André Franken Hans Neubauer Paul de Souza Therese M. Becker |
| author_facet | Sarah A. Jeffreys Branka Powter Bavanthi Balakrishnar Kelly Mok Patsy Soon André Franken Hans Neubauer Paul de Souza Therese M. Becker |
| author_sort | Sarah A. Jeffreys |
| collection | DOAJ |
| description | Therapy of hormone receptor positive breast cancer (BCa) generally targets estrogen receptor (ER) function and signaling by reducing estrogen production or by blocking its interaction with the ER. Despite good long-term responses, resistance to treatment remains a significant issue, with approximately 40% of BCa patients developing resistance to ET. Mutations in the gene encoding ERα, <i>ESR1</i>, have been identified in BCa patients and are implicated as drivers of resistance and disease recurrence. Understanding the molecular consequences of these mutations on ER protein levels and its activity, which is tightly regulated, is vital. ER activity is in part controlled via its short protein half-life and therefore changes to its stability, either through mutations or alterations in pathways involved in protein stability, may play a role in therapy resistance. Understanding these connections and how <i>ESR1</i> alterations could affect protein stability may identify novel biomarkers of resistance. This review explores the current reported data regarding posttranslational modifications (PTMs) of the ER and the potential impact of known resistance associated <i>ESR1</i> mutations on ER regulation by affecting these PTMs in the context of ET resistance. |
| first_indexed | 2024-03-10T16:24:26Z |
| format | Article |
| id | doaj.art-668bd848d82e4018be35bb985c7619ad |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T16:24:26Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-668bd848d82e4018be35bb985c7619ad2023-11-20T13:21:45ZengMDPI AGCells2073-44092020-09-0199207710.3390/cells9092077Endocrine Resistance in Breast Cancer: The Role of Estrogen Receptor StabilitySarah A. Jeffreys0Branka Powter1Bavanthi Balakrishnar2Kelly Mok3Patsy Soon4André Franken5Hans Neubauer6Paul de Souza7Therese M. Becker8Centre for Circulating Tumour Cells Diagnostics & Research, Ingham Institute of Applied Medical Research, Liverpool NSW 2170, AustraliaCentre for Circulating Tumour Cells Diagnostics & Research, Ingham Institute of Applied Medical Research, Liverpool NSW 2170, AustraliaDepartment of Medical Oncology, Liverpool Hospital, Liverpool NSW 2170, AustraliaDepartment of Medical Oncology, Liverpool Hospital, Liverpool NSW 2170, AustraliaCentre for Circulating Tumour Cells Diagnostics & Research, Ingham Institute of Applied Medical Research, Liverpool NSW 2170, AustraliaCentre for Circulating Tumour Cells Diagnostics & Research, Ingham Institute of Applied Medical Research, Liverpool NSW 2170, AustraliaDepartment of Obstetrics and Gynaecology, University Hospital and Medical Faculty of the Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, GermanyCentre for Circulating Tumour Cells Diagnostics & Research, Ingham Institute of Applied Medical Research, Liverpool NSW 2170, AustraliaCentre for Circulating Tumour Cells Diagnostics & Research, Ingham Institute of Applied Medical Research, Liverpool NSW 2170, AustraliaTherapy of hormone receptor positive breast cancer (BCa) generally targets estrogen receptor (ER) function and signaling by reducing estrogen production or by blocking its interaction with the ER. Despite good long-term responses, resistance to treatment remains a significant issue, with approximately 40% of BCa patients developing resistance to ET. Mutations in the gene encoding ERα, <i>ESR1</i>, have been identified in BCa patients and are implicated as drivers of resistance and disease recurrence. Understanding the molecular consequences of these mutations on ER protein levels and its activity, which is tightly regulated, is vital. ER activity is in part controlled via its short protein half-life and therefore changes to its stability, either through mutations or alterations in pathways involved in protein stability, may play a role in therapy resistance. Understanding these connections and how <i>ESR1</i> alterations could affect protein stability may identify novel biomarkers of resistance. This review explores the current reported data regarding posttranslational modifications (PTMs) of the ER and the potential impact of known resistance associated <i>ESR1</i> mutations on ER regulation by affecting these PTMs in the context of ET resistance.https://www.mdpi.com/2073-4409/9/9/2077breast cancer<i>ESR1</i>proteasomeposttranslational modificationsendocrine therapy |
| spellingShingle | Sarah A. Jeffreys Branka Powter Bavanthi Balakrishnar Kelly Mok Patsy Soon André Franken Hans Neubauer Paul de Souza Therese M. Becker Endocrine Resistance in Breast Cancer: The Role of Estrogen Receptor Stability Cells breast cancer <i>ESR1</i> proteasome posttranslational modifications endocrine therapy |
| title | Endocrine Resistance in Breast Cancer: The Role of Estrogen Receptor Stability |
| title_full | Endocrine Resistance in Breast Cancer: The Role of Estrogen Receptor Stability |
| title_fullStr | Endocrine Resistance in Breast Cancer: The Role of Estrogen Receptor Stability |
| title_full_unstemmed | Endocrine Resistance in Breast Cancer: The Role of Estrogen Receptor Stability |
| title_short | Endocrine Resistance in Breast Cancer: The Role of Estrogen Receptor Stability |
| title_sort | endocrine resistance in breast cancer the role of estrogen receptor stability |
| topic | breast cancer <i>ESR1</i> proteasome posttranslational modifications endocrine therapy |
| url | https://www.mdpi.com/2073-4409/9/9/2077 |
| work_keys_str_mv | AT sarahajeffreys endocrineresistanceinbreastcancertheroleofestrogenreceptorstability AT brankapowter endocrineresistanceinbreastcancertheroleofestrogenreceptorstability AT bavanthibalakrishnar endocrineresistanceinbreastcancertheroleofestrogenreceptorstability AT kellymok endocrineresistanceinbreastcancertheroleofestrogenreceptorstability AT patsysoon endocrineresistanceinbreastcancertheroleofestrogenreceptorstability AT andrefranken endocrineresistanceinbreastcancertheroleofestrogenreceptorstability AT hansneubauer endocrineresistanceinbreastcancertheroleofestrogenreceptorstability AT pauldesouza endocrineresistanceinbreastcancertheroleofestrogenreceptorstability AT theresembecker endocrineresistanceinbreastcancertheroleofestrogenreceptorstability |