Corticotropin Releasing Factor Receptors in breast cancer: Expression and activity in hormone-dependent growth in vitro

Koureta, Maria; Karaglani, Makrina; Παναγοπούλου, Μαρία; Balgkouranidou, Ioanna; Papadaki-Anastasopoulou, Artemis; Zarouchlioti, Christina; Dekavallas, Spyridon; Kolios, George; Lambropoulou, María; Baritaki, Stavroula; Chatzaki, Εkaterini

doi:10.1016/j.peptides.2020.170316

Cited by 5 publications

(7 citation statements)

References 44 publications

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“…Given that decreased methylation may lead to increased CRFR1 expression, our findings strongly support an involvement of CRFR1 signaling in CRC aggressiveness, as previously shown in mouse models where CRFR1 showed a proinflammatory and a pro-tumorigenic effect in inflammation-related colon cancer [ 63 ]. In this context, a CRFR1-mediated CRC promoting pathway has also been described in CRC cells through modulation of IL-6/JAK2/STAT3 signaling and VEGF-induced angiogenesis [ 29 ], while CRFR1 hypermethylation in breast cancer models has been associated with the expression of steroid hormone receptors, a favorable prognostic factor [ 34 ]. Overall, our findings are quite novel, given that this is the first study reporting aberrant CRFR1 methylation in CRC, as per our knowledge.…”

Section: Discussionmentioning

confidence: 99%

“…A methylation-independent assay with non-CpG bearing sites for the β-actin gene (ACTB) was used in order to verify DNA quality and normalize results. Primer sequences and qMSP conditions are presented in detail in our previous work [ 34 ]. The samples were run in duplicates.…”

Section: Methodsmentioning

confidence: 99%

“…Although the expression of CRFRs is known to be regulated by methylation in the central nervous system (CNS) [ 32 , 33 ], the methylation status of the CRFRs present in peripheral sites has not been thoroughly studied. We recently reported on an association of CRFR1 hypermethylation with the presence of steroid hormone receptors in breast cancer [ 34 ]. In addition, using genome-wide methylation approaches, Kobayashi et al found that hypermethylation of CRFR2 is correlated with colitis-induced CRC [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

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Methylation Status of Corticotropin-Releasing Factor (CRF) Receptor Genes in Colorectal Cancer

Παναγοπούλου

Cheretaki

Karaglani

et al. 2021

JCM

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The corticotropin-releasing factor (CRF) system has been strongly associated with gastrointestinal pathophysiology, including colorectal cancer (CRC). We previously showed that altered expression of CRF receptors (CRFRs) in the colon critically affects CRC progression and aggressiveness through regulation of colonic inflammation. Here, we aimed to assess the potential of CRFR methylation levels as putative biomarkers in CRC. In silico methylation analysis of CRF receptor 1 (CRFR1) and CRF receptor 2 (CRFR2) was performed using methylome data derived by CRC and Crohn’s disease (CD) tissues and CRC-derived circulating cell-free DNAs (ccfDNAs). In total, 32 and 33 differentially methylated sites of CpGs (DMCs) emerged in CRFR1 and CRFR2, respectively, between healthy and diseased tissues. The methylation patterns were verified in patient-derived ccfDNA samples by qMSP and associated with clinicopathological characteristics. An automated machine learning (AutoML) technology was applied to ccfDNA samples for classification analysis. In silico analysis revealed increased methylation of both CRFRs in CRC tissue and ccfDNA-derived datasets. CRFR1 hypermethylation was also noticed in gene body DMCs of CD patients. CRFR1 hypermethylation was further validated in CRC adjuvant-derived ccfDNA samples, whereas CRFR1 hypomethylation, observed in metastasis-derived ccfDNAs, was correlated to disease aggressiveness and adverse prognostic characteristics. AutoML analysis based on CRFRs methylation status revealed a three-feature high-performing biosignature for CRC diagnosis with an estimated AUC of 0.929. Monitoring of CRFRs methylation-based signature in CRC tissues and ccfDNAs may be of high diagnostic and prognostic significance in CRC.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Methylation Status of Corticotropin-Releasing Factor (CRF) Receptor Genes in Colorectal Cancer

Παναγοπούλου

Cheretaki

Karaglani

et al. 2021

JCM

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“…Recently, the same study group reported the in vitro detection of both CRHR1 and CRHR2 mRNAs in MCF-7 cell lines. Oestradiol exposure increased CRHR1 mRNA levels, while both CRHR2 subtypes (a and b) decreased [ 18 ]. Treatment with UCN2, a selective agonist of CRHR2, increased cancer cell migratory potential and potentiated the effects of oestradiol on migration but had no effect on proliferation [ 18 ].…”

Section: Resultsmentioning

confidence: 99%

“…Oestradiol exposure increased CRHR1 mRNA levels, while both CRHR2 subtypes (a and b) decreased [ 18 ]. Treatment with UCN2, a selective agonist of CRHR2, increased cancer cell migratory potential and potentiated the effects of oestradiol on migration but had no effect on proliferation [ 18 ]. These findings were consistent with those of Androulidaki et al .…”

Section: Resultsmentioning

confidence: 99%

The expression and possible role of corticotropin-releasing hormone family peptides and their corresponding receptors in gynaecological malignancies and premalignant conditions: a systematic review

Dimas,

Margioula-Siarkou,

Politi

et al. 2023

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The aim of this systematic review is to investigate the impact of corticotropin-releasing hormone (CRH) family peptides and their corresponding receptors on human physiology and disease onset, with a specific focus on gynaecological malignancies such as breast, endometrial, ovarian, vulvar, and cervical cancer. A comprehensive systematic review of 3 medical databases was conducted by 2 independent reviewers. We reviewed studies that explored the expression and role of CRH peptides in various aspects of cancer biology, in the context of breast, endometrial, ovarian, vulvar, and cervical cancer. Our findings reveal that CRH family peptides and their receptors, CRHR1 and CRHR2, are expressed in diverse gynaecological tissues, including cancer cells. Notably, we observed differential expression patterns among different gynaecological cancer types and stages, indicating potential associations with tumour aggressiveness and patient prognosis. Furthermore, CRH peptides were found to exert significant influences on critical cellular processes, such as cell proliferation, migration, invasion, and immune response, in gynaecological cancers. These findings highlight the multifaceted roles of CRH family peptides in gynaecological malignancies and emphasize the need for further research in this field. Therefore, understanding the mechanisms underlying the involvement of CRH family peptides in tumourigenesis may open new avenues for targeted therapeutic strategies in gynaecological malignancies.

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Critical clinical gaps in cancer precision nanomedicine development

Gan

Chan

et al. 2022

Journal of Controlled Release

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Corticotropin Releasing Factor Receptors in breast cancer: Expression and activity in hormone-dependent growth in vitro

Cited by 5 publications

References 44 publications

Methylation Status of Corticotropin-Releasing Factor (CRF) Receptor Genes in Colorectal Cancer

Methylation Status of Corticotropin-Releasing Factor (CRF) Receptor Genes in Colorectal Cancer

The expression and possible role of corticotropin-releasing hormone family peptides and their corresponding receptors in gynaecological malignancies and premalignant conditions: a systematic review

Critical clinical gaps in cancer precision nanomedicine development

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