Steroid Hormone Receptor Coregulators in Endocrine Cancers

Obeid, Jean‐Pierre; Zafar, Nawal; Hokayem, Jimmy El

doi:10.1002/iub.1517

Cited by 5 publications

(4 citation statements)

References 141 publications

(173 reference statements)

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“…Despite sharing homologous structure with each other, the three SRC members play distinct roles in many physiological and pathological processes, including development, organ function, endocrine regulation, metabolism, and tumorigenesis (13–17). Interestingly, NCOA2 is widely known for its oncogenic role, and NCOA2 gene fusions, mutations, deletions, and insertions have been observed in multiple cancers including endometrial, cancer, and pleural cancer (18, 19).…”

Section: Introductionmentioning

confidence: 99%

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Nuclear Receptor Coactivator 2 Promotes Human Breast Cancer Cell Growth by Positively Regulating the MAPK/ERK Pathway

et al. 2019

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As a member of the p160 steroid receptor coactivator (SRC) family, nuclear receptor coactivator 2 (NCOA2) is known to play essential roles in many physiological and pathological processes, including development, endocrine regulation, and tumorigenesis. However, the biological function of NCOA2 in breast cancer is not fully understood. We found that the copy number of the NCOA2 gene was frequently amplified in four breast cancers datasets, varying from 6 to 10%, and the mRNA levels of NCOA2 were also upregulated in 11% of the sequenced cases/patients (TCGA provisional dataset). Next, we confirmed that NCOA2 silencing significantly suppressed cell proliferation in different breast cancer cell lines, by inducing cell cycle arrest and apoptosis. Mechanistically, whole-transcriptome sequencing (RNA-Seq) analysis showed that NCOA2 depletion leads to downregulation of the MAPK/ERK signaling cascade, possibly via downregulating NCOA2's downstream target RASEF. In conclusion, our results suggest NCOA2 as a potential target of therapeutics against breast cancer.

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Section: Introductionmentioning

confidence: 99%

“…SRC members have also been implicated in the pathology of breast cancer (17) and gene amplification and overexpression of SRCs has been described in breast cancer previously (21–23). NCOA1 has been found to potentiate the roles of estrogen receptor (ER) and mediate transcription reprogramming in ER-positive breast cancer cells (24).…”

Section: Introductionmentioning

confidence: 99%

Nuclear Receptor Coactivator 2 Promotes Human Breast Cancer Cell Growth by Positively Regulating the MAPK/ERK Pathway

et al. 2019

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“…The main nuclear receptor activities are precisely regulated through complex and dynamic interactions of transcriptional co-regulators. Several families of coactivators and corepressors are involved in the development, progression, invasion, and therapy resistance of solid tumors, especially hormone-responsive cancers, such as breast, ovarian and prostate cancers [4] , [5] . Among the many nuclear receptor co-regulators, Receptor Interacting Protein of 140 kDa (RIP140), also called Nuclear Receptor Interacting Protein 1 (NRIP1), acts predominantly as a corepressor [6] , [7] , [8] , [9] through recruitment of histone deacetylase (HDAC) and C-terminal binding proteins (CtBPs) [10] , [11] .…”

Section: Introductionmentioning

confidence: 99%

Importance of RIP140 and LCoR Sub-Cellular Localization for Their Association With Breast Cancer Aggressiveness and Patient Survival

Sixou

Müller

Jalaguier

et al. 2018

Translational Oncology

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New markers are needed to improve diagnosis and to personalize treatments for patients with breast cancer (BC). Receptor-interacting protein of 140 kDa (RIP140) and ligand-dependent corepressor (LCoR), two transcriptional co-regulators of estrogen receptors, strongly interact in BC cells. Although their role in cancer progression has been outlined in the last few years, their function in BC has not been elucidated yet. In this study, we investigated RIP140 and LCoR localization (cytoplasm vs nucleus) in BC samples from a well-characterized cohort of patients (n = 320). RIP140 and LCoR were expressed in more than 80% of tumors, (predominantly in the cytoplasm), and the two markers were highly correlated. Expression of RIP140 and LCoR in the nucleus was negatively correlated with tumor size. Conversely, RIP140 and LCoR cytoplasmic expression strongly correlated with expression of two tumor aggressiveness markers: N-cadherin and CD133 (epithelial mesenchymal transition and cancer stem cell markers, respectively). Finally, high RIP140 nuclear expression was significantly correlated with longer overall survival, whereas high total or cytoplasmic expression of RIP140 was associated with shorter disease-free survival. Our study strongly suggests that the role of RIP140 and LCoR in BC progression could vary according to their prevalent sub-cellular localization, with opposite prognostic values for nuclear and cytoplasmic expression. The involvement in BC progression/invasiveness of cytoplasmic RIP140 could be balanced by the anti-tumor action of nuclear RIP140, thus explaining the previous contradictory findings about its role in BC.

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“…This, in turn, initiates the SHR-driven transcriptional regulation of a target gene (4,8). The ligand-induced conformational modification of a SHR also facilitates its association/dissociation with coregulator complexes, during the course of transcription (4,8,12,14).…”

Section: Classical Mode Of Shr Functionsmentioning

confidence: 99%

Steroid Hormone Receptors: Links With Cell Cycle Machinery and Breast Cancer Progression

2021

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Progression of cells through cell cycle consists of a series of events orchestrated in a regulated fashion. Such processes are influenced by cell cycle regulated expression of various proteins where multiple families of transcription factors take integral parts. Among these, the steroid hormone receptors (SHRs) represent a connection between the external hormone milieu and genes that control cellular proliferation. Therefore, understanding the molecular connection between the transcriptional role of steroid hormone receptors and cell cycle deserves importance in dissecting cellular proliferation in normal as well as malignant conditions. Deregulation of cell cycle promotes malignancies of various origins, including breast cancer. Indeed, SHR members play crucial role in breast cancer progression as well as management. This review focuses on SHR-driven cell cycle regulation and moving forward, attempts to discuss the role of SHR-driven crosstalk between cell cycle anomalies and breast cancer.

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Steroid Hormone Receptor Coregulators in Endocrine Cancers

Cited by 5 publications

References 141 publications

Nuclear Receptor Coactivator 2 Promotes Human Breast Cancer Cell Growth by Positively Regulating the MAPK/ERK Pathway

Nuclear Receptor Coactivator 2 Promotes Human Breast Cancer Cell Growth by Positively Regulating the MAPK/ERK Pathway

Importance of RIP140 and LCoR Sub-Cellular Localization for Their Association With Breast Cancer Aggressiveness and Patient Survival

Steroid Hormone Receptors: Links With Cell Cycle Machinery and Breast Cancer Progression

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