Cancers, Vol. 11, Pages 1201: Progesterone Receptor B signaling Reduces Breast Cancer Cell Aggressiveness: Role of Cyclin-D1/Cdk4 Mediating Paxillin Phosphorylation
Cancers, Vol. 11, Pages 1201: Progesterone Receptor B signaling Reduces Breast Cancer Cell Aggressiveness: Role of Cyclin-D1/Cdk4 Mediating Paxillin Phosphorylation
Cancers doi: 10.3390/cancers11081201
Authors:
Francesca Ida Montalto
Francesca Giordano
Chiara Chiodo
Stefania Marsico
Loredana Mauro
Diego Sisci
Saveria Aquila
Marilena Lanzino
Maria Luisa Panno
Sebastiano Andò
Francesca De Amicis
Progesterone-Receptor (PR) positivity is related with an enhanced response to breast cancer therapy, conversely cyclin D1 (CD1) is a retained marker of poor outcome. Herein, we demonstrate that hydroxyprogesterone (OHPg) through progesterone receptor B (PR-B) reduces breast cancer cell aggressiveness, by targeting the cytoplasmic CD1. Specifically, OHPg diminishes CD1 expression by a transcriptional regulation due to the recruitment of PR-B at a canonical half-PRE site of the CD1 promoter, together with HDAC1, determining a chromatin conformation less prone for gene transcription. CD1, together with its kinase partner Cdk4, regulates cell migration and metastasis, through the association with key components of focal adhesion, such as Paxillin (Pxn). Kaplan-Meier analysis shows that low Pxn expression was associated with increased distant metastasis-free survival in luminal A PR+ breast carcinomas. Interestingly, OHPg treatment reduced Pxn content in T47-D and MCF-7 cells; besides, the interaction between endogenous cytoplasmic CD1/Cdk4 with Pxn was reduced. ...
Source: Cancers - Category: Cancer & Oncology Authors: Francesca Ida Montalto Francesca Giordano Chiara Chiodo Stefania Marsico Loredana Mauro Diego Sisci Saveria Aquila Marilena Lanzino Maria Luisa Panno Sebastiano And ò Francesca De Amicis Tags: Article Source Type: research
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