Association of Structural Maintenance of Chromosome-1A Phosphorylation with Progression of Breast Cancer
Structural maintenance of chromosome-1A (SMC1A) is overexpressed in various malignancies including triple-negative breast cancer (TNBC). As a core component of the cohesin complex, SMC1A was initially recognized for its involvement in chromosomal cohesion and DNA-repair pathways. However, recent stu...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/14/2/128 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832588827518042112 |
|---|---|
| author | Sushma Yadav Claudia M. Kowolik Daniel Schmolze Yuan Yuan Min Lin Arthur D. Riggs David A. Horne |
| author_facet | Sushma Yadav Claudia M. Kowolik Daniel Schmolze Yuan Yuan Min Lin Arthur D. Riggs David A. Horne |
| author_sort | Sushma Yadav |
| collection | DOAJ |
| description | Structural maintenance of chromosome-1A (SMC1A) is overexpressed in various malignancies including triple-negative breast cancer (TNBC). As a core component of the cohesin complex, SMC1A was initially recognized for its involvement in chromosomal cohesion and DNA-repair pathways. However, recent studies have unveiled its pivotal role in epithelial–mesenchymal transition (EMT), metastasis, and chemo- and radio-resistance in cancer cells. In hepatocellular carcinoma, aberrant phosphorylation of SMC1A has been associated with enhanced cell proliferation and migration. Despite these insights, the precise role of SMC1A phosphorylation in breast cancer remains largely unexplored. This study represents the first investigation to test the phosphorylation status and subcellular localization of SMC1A (p-SMC1A) in breast cancer and normal breast tissues. Immunohistochemical (IHC) staining was conducted using previously validated phospho-SMC1A antibodies on a histological section and tissue microarray (TMA) comprising samples from primary, invasive, and metastatic breast cancer and normal breast tissues. Our results revealed that p-SMC1A staining intensity was lower in normal breast tissues compared to invasive or metastatic breast cancer tissues (<i>p</i> < 0.001). Approximately 40% of breast cancer tissue exhibited cytoplasmic/membranous localization of p-SMC1A, whereas nuclear expression was observed in normal breast tissues. Moreover, elevated phosphorylation levels were significantly associated with higher tumor grade and metastasis. |
| format | Article |
| id | doaj-art-21e706aec3d34785ae2c3a420538c6da |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-21e706aec3d34785ae2c3a420538c6da2025-01-24T13:26:47ZengMDPI AGCells2073-44092025-01-0114212810.3390/cells14020128Association of Structural Maintenance of Chromosome-1A Phosphorylation with Progression of Breast CancerSushma Yadav0Claudia M. Kowolik1Daniel Schmolze2Yuan Yuan3Min Lin4Arthur D. Riggs5David A. Horne6Department of Cancer Biology and Molecular Medicine, City of Hope National Medical Center, Duarte, CA 91010, USADepartment of Cancer Biology and Molecular Medicine, City of Hope National Medical Center, Duarte, CA 91010, USADepartment of Pathology, City of Hope National Medical Center, Duarte, CA 91010, USABreast Oncology, Cedars-Sinai Cancer Medical Center, Los Angeles, CA 90048, USADepartment of Cancer Biology and Molecular Medicine, City of Hope National Medical Center, Duarte, CA 91010, USADiabetes and Metabolism Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USADepartment of Cancer Biology and Molecular Medicine, City of Hope National Medical Center, Duarte, CA 91010, USAStructural maintenance of chromosome-1A (SMC1A) is overexpressed in various malignancies including triple-negative breast cancer (TNBC). As a core component of the cohesin complex, SMC1A was initially recognized for its involvement in chromosomal cohesion and DNA-repair pathways. However, recent studies have unveiled its pivotal role in epithelial–mesenchymal transition (EMT), metastasis, and chemo- and radio-resistance in cancer cells. In hepatocellular carcinoma, aberrant phosphorylation of SMC1A has been associated with enhanced cell proliferation and migration. Despite these insights, the precise role of SMC1A phosphorylation in breast cancer remains largely unexplored. This study represents the first investigation to test the phosphorylation status and subcellular localization of SMC1A (p-SMC1A) in breast cancer and normal breast tissues. Immunohistochemical (IHC) staining was conducted using previously validated phospho-SMC1A antibodies on a histological section and tissue microarray (TMA) comprising samples from primary, invasive, and metastatic breast cancer and normal breast tissues. Our results revealed that p-SMC1A staining intensity was lower in normal breast tissues compared to invasive or metastatic breast cancer tissues (<i>p</i> < 0.001). Approximately 40% of breast cancer tissue exhibited cytoplasmic/membranous localization of p-SMC1A, whereas nuclear expression was observed in normal breast tissues. Moreover, elevated phosphorylation levels were significantly associated with higher tumor grade and metastasis.https://www.mdpi.com/2073-4409/14/2/128structural maintenance of chromosome-1Aphosphorylationtumor progressionmetastasisbreast cancerimmunohistochemistry |
| spellingShingle | Sushma Yadav Claudia M. Kowolik Daniel Schmolze Yuan Yuan Min Lin Arthur D. Riggs David A. Horne Association of Structural Maintenance of Chromosome-1A Phosphorylation with Progression of Breast Cancer Cells structural maintenance of chromosome-1A phosphorylation tumor progression metastasis breast cancer immunohistochemistry |
| title | Association of Structural Maintenance of Chromosome-1A Phosphorylation with Progression of Breast Cancer |
| title_full | Association of Structural Maintenance of Chromosome-1A Phosphorylation with Progression of Breast Cancer |
| title_fullStr | Association of Structural Maintenance of Chromosome-1A Phosphorylation with Progression of Breast Cancer |
| title_full_unstemmed | Association of Structural Maintenance of Chromosome-1A Phosphorylation with Progression of Breast Cancer |
| title_short | Association of Structural Maintenance of Chromosome-1A Phosphorylation with Progression of Breast Cancer |
| title_sort | association of structural maintenance of chromosome 1a phosphorylation with progression of breast cancer |
| topic | structural maintenance of chromosome-1A phosphorylation tumor progression metastasis breast cancer immunohistochemistry |
| url | https://www.mdpi.com/2073-4409/14/2/128 |
| work_keys_str_mv | AT sushmayadav associationofstructuralmaintenanceofchromosome1aphosphorylationwithprogressionofbreastcancer AT claudiamkowolik associationofstructuralmaintenanceofchromosome1aphosphorylationwithprogressionofbreastcancer AT danielschmolze associationofstructuralmaintenanceofchromosome1aphosphorylationwithprogressionofbreastcancer AT yuanyuan associationofstructuralmaintenanceofchromosome1aphosphorylationwithprogressionofbreastcancer AT minlin associationofstructuralmaintenanceofchromosome1aphosphorylationwithprogressionofbreastcancer AT arthurdriggs associationofstructuralmaintenanceofchromosome1aphosphorylationwithprogressionofbreastcancer AT davidahorne associationofstructuralmaintenanceofchromosome1aphosphorylationwithprogressionofbreastcancer |