Effect of p53 and its N‐terminally truncated isoform, Δ40p53, on breast cancer migration and invasion
Breast cancer is the most diagnosed malignancy in women, with over half a million women dying from this disease each year. In our previous studies, ∆40p53, an N‐terminally truncated p53 isoform, was found to be upregulated in breast cancers, and a high ∆40p53 : p53α ratio was linked with worse disea...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-01-01
|
| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.13118 |
| _version_ | 1819007759834677248 |
|---|---|
| author | Xiajie Zhang Kira Groen Brianna C. Morten Luiza Steffens Reinhardt Hamish G. Campbell Antony W. Braithwaite Jean‐Christophe Bourdon Kelly A. Avery‐Kiejda |
| author_facet | Xiajie Zhang Kira Groen Brianna C. Morten Luiza Steffens Reinhardt Hamish G. Campbell Antony W. Braithwaite Jean‐Christophe Bourdon Kelly A. Avery‐Kiejda |
| author_sort | Xiajie Zhang |
| collection | DOAJ |
| description | Breast cancer is the most diagnosed malignancy in women, with over half a million women dying from this disease each year. In our previous studies, ∆40p53, an N‐terminally truncated p53 isoform, was found to be upregulated in breast cancers, and a high ∆40p53 : p53α ratio was linked with worse disease‐free survival. Although p53α inhibits cancer migration and invasion, little is known about the role of ∆40p53 in regulating these metastasis‐related processes and its role in contributing to worse prognosis. The aim of this study was to assess the role of ∆40p53 in breast cancer migration and invasion. A relationship between Δ40p53 and gene expression profiles was identified in oestrogen‐receptor‐positive breast cancer specimens. To further evaluate the role of Δ40p53 in oestrogen‐receptor‐positive breast cancer, MCF‐7 and ZR75‐1 cell lines were transduced to knockdown p53α or Δ40p53 and overexpress Δ40p53. Proliferation, migration and invasion were assessed in the transduced sublines, and gene expression was assessed through RNA‐sequencing and validated by reverse‐transcription quantitative PCR. Knockdown of both p53α and ∆40p53 resulted in increased proliferation, whereas overexpression of ∆40p53 reduced proliferation rates. p53α knockdown was also associated with increased cell mobility. ∆40p53 overexpression reduced both migratory and invasive properties of the transduced cells. Phenotypic findings are supported by gene expression data, including differential expression of LRG1, HYOU1, UBE2QL1, SERPINA5 and PCDH7. Taken together, these results suggest that, at the basal level, ∆40p53 works similarly to p53α in suppressing cellular mobility and proliferation, although the role of Δ40p53 may be cell context‐specific. |
| first_indexed | 2024-12-21T00:29:41Z |
| format | Article |
| id | doaj.art-d096e9855e9f4682af97e433816271a0 |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-12-21T00:29:41Z |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-d096e9855e9f4682af97e433816271a02022-12-21T19:21:55ZengWileyMolecular Oncology1574-78911878-02612022-01-0116244746510.1002/1878-0261.13118Effect of p53 and its N‐terminally truncated isoform, Δ40p53, on breast cancer migration and invasionXiajie Zhang0Kira Groen1Brianna C. Morten2Luiza Steffens Reinhardt3Hamish G. Campbell4Antony W. Braithwaite5Jean‐Christophe Bourdon6Kelly A. Avery‐Kiejda7Hunter Medical Research Institute New Lambton Heights NSW AustraliaHunter Medical Research Institute New Lambton Heights NSW AustraliaHunter Medical Research Institute New Lambton Heights NSW AustraliaHunter Medical Research Institute New Lambton Heights NSW AustraliaChildren’s Medical Research Institute University of Sydney NSW AustraliaChildren’s Medical Research Institute University of Sydney NSW AustraliaDundee Cancer Centre Ninewells Hospital and Medical School University of Dundee UKHunter Medical Research Institute New Lambton Heights NSW AustraliaBreast cancer is the most diagnosed malignancy in women, with over half a million women dying from this disease each year. In our previous studies, ∆40p53, an N‐terminally truncated p53 isoform, was found to be upregulated in breast cancers, and a high ∆40p53 : p53α ratio was linked with worse disease‐free survival. Although p53α inhibits cancer migration and invasion, little is known about the role of ∆40p53 in regulating these metastasis‐related processes and its role in contributing to worse prognosis. The aim of this study was to assess the role of ∆40p53 in breast cancer migration and invasion. A relationship between Δ40p53 and gene expression profiles was identified in oestrogen‐receptor‐positive breast cancer specimens. To further evaluate the role of Δ40p53 in oestrogen‐receptor‐positive breast cancer, MCF‐7 and ZR75‐1 cell lines were transduced to knockdown p53α or Δ40p53 and overexpress Δ40p53. Proliferation, migration and invasion were assessed in the transduced sublines, and gene expression was assessed through RNA‐sequencing and validated by reverse‐transcription quantitative PCR. Knockdown of both p53α and ∆40p53 resulted in increased proliferation, whereas overexpression of ∆40p53 reduced proliferation rates. p53α knockdown was also associated with increased cell mobility. ∆40p53 overexpression reduced both migratory and invasive properties of the transduced cells. Phenotypic findings are supported by gene expression data, including differential expression of LRG1, HYOU1, UBE2QL1, SERPINA5 and PCDH7. Taken together, these results suggest that, at the basal level, ∆40p53 works similarly to p53α in suppressing cellular mobility and proliferation, although the role of Δ40p53 may be cell context‐specific.https://doi.org/10.1002/1878-0261.13118breast cancergene expressionmigration and invasionp53Δ40p53 |
| spellingShingle | Xiajie Zhang Kira Groen Brianna C. Morten Luiza Steffens Reinhardt Hamish G. Campbell Antony W. Braithwaite Jean‐Christophe Bourdon Kelly A. Avery‐Kiejda Effect of p53 and its N‐terminally truncated isoform, Δ40p53, on breast cancer migration and invasion Molecular Oncology breast cancer gene expression migration and invasion p53 Δ40p53 |
| title | Effect of p53 and its N‐terminally truncated isoform, Δ40p53, on breast cancer migration and invasion |
| title_full | Effect of p53 and its N‐terminally truncated isoform, Δ40p53, on breast cancer migration and invasion |
| title_fullStr | Effect of p53 and its N‐terminally truncated isoform, Δ40p53, on breast cancer migration and invasion |
| title_full_unstemmed | Effect of p53 and its N‐terminally truncated isoform, Δ40p53, on breast cancer migration and invasion |
| title_short | Effect of p53 and its N‐terminally truncated isoform, Δ40p53, on breast cancer migration and invasion |
| title_sort | effect of p53 and its n terminally truncated isoform δ40p53 on breast cancer migration and invasion |
| topic | breast cancer gene expression migration and invasion p53 Δ40p53 |
| url | https://doi.org/10.1002/1878-0261.13118 |
| work_keys_str_mv | AT xiajiezhang effectofp53anditsnterminallytruncatedisoformd40p53onbreastcancermigrationandinvasion AT kiragroen effectofp53anditsnterminallytruncatedisoformd40p53onbreastcancermigrationandinvasion AT briannacmorten effectofp53anditsnterminallytruncatedisoformd40p53onbreastcancermigrationandinvasion AT luizasteffensreinhardt effectofp53anditsnterminallytruncatedisoformd40p53onbreastcancermigrationandinvasion AT hamishgcampbell effectofp53anditsnterminallytruncatedisoformd40p53onbreastcancermigrationandinvasion AT antonywbraithwaite effectofp53anditsnterminallytruncatedisoformd40p53onbreastcancermigrationandinvasion AT jeanchristophebourdon effectofp53anditsnterminallytruncatedisoformd40p53onbreastcancermigrationandinvasion AT kellyaaverykiejda effectofp53anditsnterminallytruncatedisoformd40p53onbreastcancermigrationandinvasion |