2026-04-29T04:09:57Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/159272024-09-21T12:42:06Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Serrano-López, Emilio M
author
Coronado-Parra, Teresa
author
Marín-Vicente, Consuelo
author
Szallasi, Zoltan
author
Gómez-Abellán, Victoria
author
López-Andreo, María José
author
Gragera, Marcos
author
Gómez-Fernández, Juan C
author
López-Nicolás, Rubén
author
Corbalán-García, Senena
funder
Fundación Séneca-Agencia de Ciencia y Tecnología de la Región de Murcia
2023-04-27T12:24:05Z
2023-04-27T12:24:05Z
2022-11-14
Int J Mol Sci. 2022 Nov 14;23(22):14023.
http://hdl.handle.net/20.500.12105/15927
36430510
10.3390/ijms232214023
1422-0067
International journal of molecular sciences
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.
eng
Deciphering the Role and Signaling Pathways of PKCα in Luminal A Breast Cancer Cells.
journal article
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Deciphering the Role Int J Mol Sci 2022.pdf
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Deciphering the Role Int J Mol Sci 2022.pdf.txt