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CCM signaling complex (CSC) couples both classic and non-classic Progesterone receptor signaling.
Abou-Fadel, Johnathan; Jiang, Xiaoting; Grajeda, Brian; Padarti, Akhil; Ellis, Cameron C; Flores, Esmeralda; Cailing-De La O, Alyssa-Marie D; Zhang, Jun.
Afiliación
  • Abou-Fadel J; Department of Molecular and Translational Medicine (MTM), Texas Tech University Health Science Center El Paso, 5001 El Paso Drive, El Paso, TX, 79905, USA.
  • Jiang X; Department of Molecular and Translational Medicine (MTM), Texas Tech University Health Science Center El Paso, 5001 El Paso Drive, El Paso, TX, 79905, USA.
  • Grajeda B; Department of Biological Sciences, University of Texas at El Paso, El Paso, TX, 79902, USA.
  • Padarti A; Department of Molecular and Translational Medicine (MTM), Texas Tech University Health Science Center El Paso, 5001 El Paso Drive, El Paso, TX, 79905, USA.
  • Ellis CC; Department of Biological Sciences, University of Texas at El Paso, El Paso, TX, 79902, USA.
  • Flores E; Department of Molecular and Translational Medicine (MTM), Texas Tech University Health Science Center El Paso, 5001 El Paso Drive, El Paso, TX, 79905, USA.
  • Cailing-De La O AD; Department of Molecular and Translational Medicine (MTM), Texas Tech University Health Science Center El Paso, 5001 El Paso Drive, El Paso, TX, 79905, USA.
  • Zhang J; Department of Molecular and Translational Medicine (MTM), Texas Tech University Health Science Center El Paso, 5001 El Paso Drive, El Paso, TX, 79905, USA. jun.zhang2000@gmail.com.
Cell Commun Signal ; 20(1): 120, 2022 08 15.
Article en En | MEDLINE | ID: mdl-35971177
BACKGROUND: Breast cancer, the most diagnosed cancer, remains the second leading cause of cancer death in the United States, and excessive Progesterone (PRG) or Mifepristone (MIF) exposure may be at an increased risk for developing breast cancer. PRG exerts its cellular responses through signaling cascades involving classic, non-classic, or combined responses by binding to either classic nuclear PRG receptors (nPRs) or non-classic membrane PRG receptors (mPRs). Currently, the intricate balance and switch mechanisms between these two signaling cascades remain elusive. Three genes, CCM1-3, form the CCM signaling complex (CSC) which mediates multiple signaling cascades. METHODS: Utilizing molecular, cellular, Omics, and systems biology approaches, we analyzed the relationship among the CSC, PRG, and nPRs/mPRs during breast cancer tumorigenesis. RESULTS: We discovered that the CSC plays an essential role in coupling both classic and non-classic PRG signaling pathways by mediating crosstalk between them, forming the CmPn (CSC-mPRs-PRG-nPRs) signaling network. We found that mPR-specific PRG actions (PRG + MIF) play an essential role in this CmPn network during breast cancer tumorigenesis. Additionally, we have identified 4 categories of candidate biomarkers (9 intrinsic, 2 PRG-inducible, 1 PRG-repressive, 1 mPR-specific PRG-repressive, and 2 mPR-responsive) for Luminal-A breast cancers during tumorigenesis and have confirmed the prognostic application of RPL13 and RPL38 as intrinsic biomarkers using a dual validation method. CONCLUSIONS: We have discovered that the CSC plays an essential role in the CmPn signaling network for Luminal-A breast cancers with identification of two intrinsic biomarkers. Video Abstract.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Receptores de Progesterona Límite: Female / Humans Idioma: En Revista: Cell Commun Signal Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Imprimir
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Receptores de Progesterona Límite: Female / Humans Idioma: En Revista: Cell Commun Signal Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido