Cortisol-induced SRSF3 expression promotes GR splicing, RACK1 expression and breast cancer cells migration

Buoso, Erica; Ronfani, Melania; Galasso, Marilisa; Ventura, Denise; Corsini, Emanuela; Racchi, Marco

doi:10.1016/j.phrs.2019.03.008

Cited by 31 publications

(35 citation statements)

References 55 publications

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“…Breast cancer (BC) is a heterogeneous disease due to variable histological subtypes and differences in response to therapy and clinical outcome 1 . In human BC cells, the receptor for activated C kinase 1 (RACK1) has been identified as a possible prognostic marker and drug target 2 due to its critical role in cancer cell migration and invasion [3][4][5][6] . Changes in RACK1 levels have been found to subvert physiological functions, leading to the development and maintenance of several BC hallmarks [6][7][8][9] .…”

Section: Introductionmentioning

confidence: 99%

“…A complex hormonal balance between glucocorticoids and androgens has been demonstrated to control RACK1 expression in both the immune [11][12][13][14][15][16] and the cancer context 5,9 . Consequently, based on the hormone-related nature of many BC types, a deeper understanding of RACK1 transcriptional regulation is of pivotal interest 17 .…”

Section: Introductionmentioning

confidence: 99%

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OXER1 and RACK1-associated pathway: a promising drug target for breast cancer progression

et al. 2020

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Recent data indicate that receptor for activated C kinase 1 (RACK1) is a putative prognostic marker and drug target in breast cancer (BC). High RACK1 expression is negatively associated with overall survival, as it seems to promote BC progression. In tumors, RACK1 expression is controlled by a complex balance between glucocorticoids and androgens. Given the fact that androgens and androgenic derivatives can inhibit BC cell proliferation and migration, the role of androgen signaling in regulating RACK1 transcription in mammary tumors is of pivotal interest. Here, we provide evidence that nandrolone (19-nortosterone) inhibits BC cell proliferation and migration by antagonizing the PI3K/Akt/NF-κB signaling pathway, which eventually results in RACK1 downregulation. We also show that nandrolone impairs the PI3K/Akt/NF-κB signaling pathway and decreases RACK1 expression via binding to the membrane-bound receptor, oxoeicosanoid receptor 1 (OXER1). High levels of OXER1 are observed in several BC cell lines and correlate with RACK1 expression and poor prognosis. Our data provide evidence on the role played by the OXER1-dependent intracellular pathway in BC progression and shed light on the mechanisms underlying membrane-dependent androgen effects on RACK1 regulation. Besides the mechanistic relevance, the results of the study are of interest from a translational prospective. In fact, they identify a new and actionable pathway to be used for the design of innovative and rational therapeutic strategies in the context of the personalized treatment of BC. In addition, they draw attention on nandrolone-based compounds that lack hormonal activity as potential anti-tumor agents.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

OXER1 and RACK1-associated pathway: a promising drug target for breast cancer progression

et al. 2020

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“…TNBC is a sub-type of breast cancer with ER-deficiency, HER2-decificiency, and PR-deficiency features 39,40 . Although the molecular targeting agents have been applied, the clinical outcomes and the prognosis of patients with TNBC are still poor 41,42 .…”

Section: Discussionmentioning

confidence: 99%

FBI-1 enhanced the resistance of triple-negative breast cancer cells to chemotherapeutic agents via the miR-30c/PXR axis

Yang

Ren²,

Wang³

et al. 2020

Cell Death Dis

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The factor that binds to the inducer of short transcripts‐1 (FBI-1) is a transcription suppressor and an important proto‐oncogene that plays multiple roles in carcinogenesis and therapeutic resistance. In the present work, our results indicated that FBI-1 enhanced the resistance of triple-negative breast cancer (TNBC) cells to chemotherapeutic agents by repressing the expression of micoRNA-30c targeting the pregnane X receptor (PXR). The expression of FBI-1 was positively related to PXR and its downstream drug resistance-related genes in TNBC tissues. FBI-1 enhanced the expression of PXR and enhanced the activation of the PXR pathway. The miR-30c decreased the expression of PXR by targeting the 3′-UTR of PXR, and FBI-1 increased the expression of PXR by repressing miR-30c’s expression. Through the miR-30c/PXR axis, FBI-1 accelerated the clearance or elimination of antitumor agents in TNBC cells (the TNBC cell lines or the patients derived cells [PDCs]) and induced the resistance of cells to antitumor agents. Therefore, the results indicated that the miR-30c/PXR axis participates in the FBI-1-mediated drug-resistance of TNBC cells.

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“…It was shown that using 12 such isoforms as biomarkers can distinguish a breast cancer tumor from normal tissue and moreover specify the grade level of the tumor [32]. Many splicing factors have been shown to have a role in breast cancer and to promote its progression, including SRSF1 [30,47,48], SRSF3 [49], SRSF5 [50], SRSF6 [40][41][42], SRSF10 [51], HNRNPA1 [33], HNRNPA2B1 [34,35,52], HNRNPM [53], HNRNPK [36,37], HNRNPL [54], RBFOX2 [55], ESRP1/2 [55], PTBP1 [38,39] RBM5/10 [56], Sam68 [57] and FOX2 [58]. Since our sequencing of saliva RNA identified 28 splicing factors out of the known 71, we focused on this group as a possible marker.…”

Section: Discussionmentioning

confidence: 99%

Splicing Factor Transcript Abundance in Saliva as a Diagnostic Tool for Breast Cancer

Bentata

Morgenstern

Nevo

et al. 2020

Genes

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Breast cancer is the second leading cause of death in women above 60 years in the US. Screening mammography is recommended for women above 50 years; however, 22% of breast cancer cases are diagnosed in women below this age. We set out to develop a test based on the detection of cell-free RNA from saliva. To this end, we sequenced RNA from a pool of ten women. The 1254 transcripts identified were enriched for genes with an annotation of alternative pre-mRNA splicing. Pre-mRNA splicing is a tightly regulated process and its misregulation in cancer cells promotes the formation of cancer-driving isoforms. For these reasons, we chose to focus on splicing factors as biomarkers for the early detection of breast cancer. We found that the level of the splicing factors is unique to each woman and consistent in the same woman at different time points. Next, we extracted RNA from 36 healthy subjects and 31 breast cancer patients. Recording the mRNA level of seven splicing factors in these samples demonstrated that the combination of all these factors is different in the two groups (p value = 0.005). Our results demonstrate a differential abundance of splicing factor mRNA in the saliva of breast cancer patients.

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Cortisol-induced SRSF3 expression promotes GR splicing, RACK1 expression and breast cancer cells migration

Cited by 31 publications

References 55 publications

OXER1 and RACK1-associated pathway: a promising drug target for breast cancer progression

OXER1 and RACK1-associated pathway: a promising drug target for breast cancer progression

FBI-1 enhanced the resistance of triple-negative breast cancer cells to chemotherapeutic agents via the miR-30c/PXR axis

Splicing Factor Transcript Abundance in Saliva as a Diagnostic Tool for Breast Cancer

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