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Selective loss of phosphoserine aminotransferase 1 (PSAT1) suppresses migration, invasion, and experimental metastasis in triple negative breast cancer.

Abstract

Breast cancer is the second leading cause of cancer-related deaths among women and 90% of these mortalities can be attributed to progression to metastatic disease. In particular, triple negative breast cancer (TNBC) is extremely aggressive and frequently metastasizes to multiple organs. As TNBCs are categorized by their lack of hormone receptors, these tumors are very heterogeneous and are immune to most targeted therapies. Metabolic changes are observed in the majority of TNBC and a large proportion upregulate enzymes within the serine synthesis pathway, including phosphoserine aminotransferase 1 (PSAT1). In this report, we investigate the role of PSAT1 in migration and invasion potential in a subset of TNBC cell types. We found that the expression of PSAT1 increases with TNBC clinical grade. We also demonstrate that suppression of PSAT1 or phosphoglycerate dehydrogenase (PHGDH) does not negatively impact cell proliferation in TNBC cells that are not dependent on de novo serine synthesis. However, we observed that suppression of PSAT1 specifically alters the F-actin cytoskeletal arrangement and morphology in these TNBC cell lines. In addition, suppression of PSAT1 inhibits motility and migration in these TNBC cell lines, which is not recapitulated upon loss of PHGDH. PSAT1 silencing also reduced the number of lung tumor nodules in a model of experimental metastasis; yet did not decrease anchorage-independent growth. Together, these results suggest that PSAT1 functions to drive migratory potential in promoting metastasis in select TNBC cells independent of its role in serine synthesis.

Authors+Show Affiliations

Department of Biochemistry and Molecular Genetics, University of Louisville, Louisville, KY, USA.Department of Biochemistry and Molecular Genetics, University of Louisville, Louisville, KY, USA.Department of Biochemistry and Molecular Genetics, University of Louisville, Louisville, KY, USA. Moffitt Cancer Center, University of South Florida, Tampa, FL, USA.Department of Biochemistry and Molecular Genetics, University of Louisville, Louisville, KY, USA.Department of Biochemistry and Molecular Genetics, University of Louisville, Louisville, KY, USA.Department of Biochemistry and Molecular Genetics, University of Louisville, Louisville, KY, USA.Department of Biochemistry and Molecular Genetics, University of Louisville, Louisville, KY, USA. bfclem01@louisville.edu. James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA. bfclem01@louisville.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31630284

Citation

Metcalf, Stephanie, et al. "Selective Loss of Phosphoserine Aminotransferase 1 (PSAT1) Suppresses Migration, Invasion, and Experimental Metastasis in Triple Negative Breast Cancer." Clinical & Experimental Metastasis, 2019.
Metcalf S, Dougherty S, Kruer T, et al. Selective loss of phosphoserine aminotransferase 1 (PSAT1) suppresses migration, invasion, and experimental metastasis in triple negative breast cancer. Clin Exp Metastasis. 2019.
Metcalf, S., Dougherty, S., Kruer, T., Hasan, N., Biyik-Sit, R., Reynolds, L., & Clem, B. F. (2019). Selective loss of phosphoserine aminotransferase 1 (PSAT1) suppresses migration, invasion, and experimental metastasis in triple negative breast cancer. Clinical & Experimental Metastasis, doi:10.1007/s10585-019-10000-7.
Metcalf S, et al. Selective Loss of Phosphoserine Aminotransferase 1 (PSAT1) Suppresses Migration, Invasion, and Experimental Metastasis in Triple Negative Breast Cancer. Clin Exp Metastasis. 2019 Oct 19; PubMed PMID: 31630284.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Selective loss of phosphoserine aminotransferase 1 (PSAT1) suppresses migration, invasion, and experimental metastasis in triple negative breast cancer. AU - Metcalf,Stephanie, AU - Dougherty,Susan, AU - Kruer,Traci, AU - Hasan,Nazarul, AU - Biyik-Sit,Rumeysa, AU - Reynolds,Lindsey, AU - Clem,Brian F, Y1 - 2019/10/19/ PY - 2019/04/15/received PY - 2019/09/30/accepted PY - 2019/10/21/entrez PY - 2019/10/21/pubmed PY - 2019/10/21/medline KW - Metastasis KW - PSAT1 KW - Serine synthesis KW - Triple negative breast cancer JF - Clinical & experimental metastasis JO - Clin. Exp. Metastasis N2 - Breast cancer is the second leading cause of cancer-related deaths among women and 90% of these mortalities can be attributed to progression to metastatic disease. In particular, triple negative breast cancer (TNBC) is extremely aggressive and frequently metastasizes to multiple organs. As TNBCs are categorized by their lack of hormone receptors, these tumors are very heterogeneous and are immune to most targeted therapies. Metabolic changes are observed in the majority of TNBC and a large proportion upregulate enzymes within the serine synthesis pathway, including phosphoserine aminotransferase 1 (PSAT1). In this report, we investigate the role of PSAT1 in migration and invasion potential in a subset of TNBC cell types. We found that the expression of PSAT1 increases with TNBC clinical grade. We also demonstrate that suppression of PSAT1 or phosphoglycerate dehydrogenase (PHGDH) does not negatively impact cell proliferation in TNBC cells that are not dependent on de novo serine synthesis. However, we observed that suppression of PSAT1 specifically alters the F-actin cytoskeletal arrangement and morphology in these TNBC cell lines. In addition, suppression of PSAT1 inhibits motility and migration in these TNBC cell lines, which is not recapitulated upon loss of PHGDH. PSAT1 silencing also reduced the number of lung tumor nodules in a model of experimental metastasis; yet did not decrease anchorage-independent growth. Together, these results suggest that PSAT1 functions to drive migratory potential in promoting metastasis in select TNBC cells independent of its role in serine synthesis. SN - 1573-7276 UR - https://www.unboundmedicine.com/medline/citation/31630284/Selective_loss_of_phosphoserine_aminotransferase_1_(PSAT1)_suppresses_migration,_invasion,_and_experimental_metastasis_in_triple_negative_breast_cancer L2 - https://doi.org/10.1007/s10585-019-10000-7 DB - PRIME DP - Unbound Medicine ER -