Deciphering the Role and Signaling Pathways of PKCα in Luminal A Breast Cancer Cells
Protein kinase C (PKC) comprises a family of highly related serine/threonine protein kinases involved in multiple signaling pathways, which control cell proliferation, survival, and differentiation. The role of PKCα in cancer has been studied for many years. However, it has been impossible to establ...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/22/14023 |
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| author | Emilio M. Serrano-López Teresa Coronado-Parra Consuelo Marín-Vicente Zoltan Szallasi Victoria Gómez-Abellán María José López-Andreo Marcos Gragera Juan C. Gómez-Fernández Rubén López-Nicolás Senena Corbalán-García |
| author_facet | Emilio M. Serrano-López Teresa Coronado-Parra Consuelo Marín-Vicente Zoltan Szallasi Victoria Gómez-Abellán María José López-Andreo Marcos Gragera Juan C. Gómez-Fernández Rubén López-Nicolás Senena Corbalán-García |
| author_sort | Emilio M. Serrano-López |
| collection | DOAJ |
| description | Protein kinase C (PKC) comprises a family of highly related serine/threonine protein kinases involved in multiple signaling pathways, which control cell proliferation, survival, and differentiation. The role of PKCα in cancer has been studied for many years. However, it has been impossible to establish whether PKCα acts as an oncogene or a tumor suppressor. Here, we analyzed the importance of PKCα in cellular processes such as proliferation, migration, or apoptosis by inhibiting its gene expression in a luminal A breast cancer cell line (MCF-7). Differential expression analysis and phospho-kinase arrays of PKCα-KD vs. PKCα-WT MCF-7 cells identified an essential set of proteins and oncogenic kinases of the JAK/STAT and PI3K/AKT pathways that were down-regulated, whereas IGF1R, ERK1/2, and p53 were up-regulated. In addition, unexpected genes related to the interferon pathway appeared down-regulated, while PLC, ERBB4, or PDGFA displayed up-regulated. The integration of this information clearly showed us the usefulness of inhibiting a multifunctional kinase-like PKCα in the first step to control the tumor phenotype. Then allowing us to design a possible selection of specific inhibitors for the unexpected up-regulated pathways to further provide a second step of treatment to inhibit the proliferation and migration of MCF-7 cells. The results of this study suggest that PKCα plays an oncogenic role in this type of breast cancer model. In addition, it reveals the signaling mode of PKCα at both gene expression and kinase activation. In this way, a wide range of proteins can implement a new strategy to fine-tune the control of crucial functions in these cells and pave the way for designing targeted cancer therapies. |
| first_indexed | 2024-03-09T18:17:22Z |
| format | Article |
| id | doaj.art-15c72ba2bbc944ce927569469619fa53 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T18:17:22Z |
| publishDate | 2022-11-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-15c72ba2bbc944ce927569469619fa532023-11-24T08:37:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123221402310.3390/ijms232214023Deciphering the Role and Signaling Pathways of PKCα in Luminal A Breast Cancer CellsEmilio M. Serrano-López0Teresa Coronado-Parra1Consuelo Marín-Vicente2Zoltan Szallasi3Victoria Gómez-Abellán4María José López-Andreo5Marcos Gragera6Juan C. Gómez-Fernández7Rubén López-Nicolás8Senena Corbalán-García9Department of Biochemistry and Molecular Biology A, Veterinary School, Universidad de Murcia, CEIR Campus Mare Nostrum (CMN), 30100 Murcia, SpainDepartment of Biochemistry and Molecular Biology A, Veterinary School, Universidad de Murcia, CEIR Campus Mare Nostrum (CMN), 30100 Murcia, SpainDepartment of Biochemistry and Molecular Biology A, Veterinary School, Universidad de Murcia, CEIR Campus Mare Nostrum (CMN), 30100 Murcia, SpainComputational Health Informatics Program, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USADepartment of Biochemistry and Molecular Biology A, Veterinary School, Universidad de Murcia, CEIR Campus Mare Nostrum (CMN), 30100 Murcia, SpainDepartment of Biochemistry and Molecular Biology A, Veterinary School, Universidad de Murcia, CEIR Campus Mare Nostrum (CMN), 30100 Murcia, SpainDepartment of Biochemistry and Molecular Biology A, Veterinary School, Universidad de Murcia, CEIR Campus Mare Nostrum (CMN), 30100 Murcia, SpainDepartment of Biochemistry and Molecular Biology A, Veterinary School, Universidad de Murcia, CEIR Campus Mare Nostrum (CMN), 30100 Murcia, SpainDepartment of Biochemistry and Molecular Biology A, Veterinary School, Universidad de Murcia, CEIR Campus Mare Nostrum (CMN), 30100 Murcia, SpainDepartment of Biochemistry and Molecular Biology A, Veterinary School, Universidad de Murcia, CEIR Campus Mare Nostrum (CMN), 30100 Murcia, SpainProtein kinase C (PKC) comprises a family of highly related serine/threonine protein kinases involved in multiple signaling pathways, which control cell proliferation, survival, and differentiation. The role of PKCα in cancer has been studied for many years. However, it has been impossible to establish whether PKCα acts as an oncogene or a tumor suppressor. Here, we analyzed the importance of PKCα in cellular processes such as proliferation, migration, or apoptosis by inhibiting its gene expression in a luminal A breast cancer cell line (MCF-7). Differential expression analysis and phospho-kinase arrays of PKCα-KD vs. PKCα-WT MCF-7 cells identified an essential set of proteins and oncogenic kinases of the JAK/STAT and PI3K/AKT pathways that were down-regulated, whereas IGF1R, ERK1/2, and p53 were up-regulated. In addition, unexpected genes related to the interferon pathway appeared down-regulated, while PLC, ERBB4, or PDGFA displayed up-regulated. The integration of this information clearly showed us the usefulness of inhibiting a multifunctional kinase-like PKCα in the first step to control the tumor phenotype. Then allowing us to design a possible selection of specific inhibitors for the unexpected up-regulated pathways to further provide a second step of treatment to inhibit the proliferation and migration of MCF-7 cells. The results of this study suggest that PKCα plays an oncogenic role in this type of breast cancer model. In addition, it reveals the signaling mode of PKCα at both gene expression and kinase activation. In this way, a wide range of proteins can implement a new strategy to fine-tune the control of crucial functions in these cells and pave the way for designing targeted cancer therapies.https://www.mdpi.com/1422-0067/23/22/14023PKCbreast cancertargeted therapykinasessignaling pathways |
| spellingShingle | Emilio M. Serrano-López Teresa Coronado-Parra Consuelo Marín-Vicente Zoltan Szallasi Victoria Gómez-Abellán María José López-Andreo Marcos Gragera Juan C. Gómez-Fernández Rubén López-Nicolás Senena Corbalán-García Deciphering the Role and Signaling Pathways of PKCα in Luminal A Breast Cancer Cells International Journal of Molecular Sciences PKC breast cancer targeted therapy kinases signaling pathways |
| title | Deciphering the Role and Signaling Pathways of PKCα in Luminal A Breast Cancer Cells |
| title_full | Deciphering the Role and Signaling Pathways of PKCα in Luminal A Breast Cancer Cells |
| title_fullStr | Deciphering the Role and Signaling Pathways of PKCα in Luminal A Breast Cancer Cells |
| title_full_unstemmed | Deciphering the Role and Signaling Pathways of PKCα in Luminal A Breast Cancer Cells |
| title_short | Deciphering the Role and Signaling Pathways of PKCα in Luminal A Breast Cancer Cells |
| title_sort | deciphering the role and signaling pathways of pkcα in luminal a breast cancer cells |
| topic | PKC breast cancer targeted therapy kinases signaling pathways |
| url | https://www.mdpi.com/1422-0067/23/22/14023 |
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