Gene amplification of YB‐1 in castration‐resistant prostate cancer in association with aberrant androgen receptor expression

Abstract

Most prostate cancers are initially dependent on androgens for tumor growth, and show good response to androgen-deprivation therapy (ADT). 1 However, most of these cancers eventually recur during ADT in a castration-resistant manner and are defined as castration-resistant prostate cancer (CRPC). 2 Despite the recognition of a variety of molecular mechanisms for progression to castration resistance, androgen receptor (AR)-dependent mechanisms, such as AR overexpression and AR variant expression, are considered critical. 3,4 Y-box binding protein-1 (YB-1) has pleiotropic roles in the nucleus and cytoplasm as a transcription and splicing factor that modulates the expression of its target genes. 5,6 Y-box binding protein-1 was shown to be overexpressed in various cancers and involved in their treatment resistance. 5,6 In prostate cancer, YB-1 expression was reported to be

Clinical impact of HSD3B1 polymorphism by metastatic volume and somatic HSD3B1 alterations in advanced prostate cancer

“…DdPCR was performed as described previously (Shiota et al, 2021). Primers and probes for ddPCR were as follows: HSD3B1 (dHsaCNS478433216) and RPP30 (dHsaCP2500350; BioRad Laboratories).…”

Evaluation of Interaction of Some Quinolone Derivatives on RSK-4 Using a Theoretical Model

“…Some quinolone derivatives (Figure 1) were used to evaluate the possible interaction with both the androgen receptor and RSK-4 as follows: 1= 1-ethyl-2(1H)-quinolone [19] 2= 1-methyl-6-nitro-2(1H)-quinolone [20] 3= 2-(2-quinolinyl)-1-[4-(trifluoromethyl)phenyl]ethanone [21] 4= 2-chloro-1-(8-hydroxy-5-quinolinyl)ethanone [22] 5= 2-cyano-3-phenyl-N-(quinoline-3-yl)acrylamide [23] 6= 4-chloro-6-(3,4-dihydro-1(2h)-quinolinyl)-2-pyrimidinamine [24] 7= 4-cyclohexyl-2(1h)-quinolone [25] 8= 4-Hydroxy-1-methyl-2(1H)-quinolone [26] 9= 5,7-dibromo-8-quinolinyl 4-nitrobenzoate [27] 10=6-methoxy-8-[(2-furanylmethyl)amino]-4-methyl-5-(3trifluoromethylphenyloxy)quinolone [28] 11= 6-Quinolinyl trifluoromethanesulfonate [29] 12= 8-(Bromomethyl)quinoline [30] 13= 8-quinolinyl n-(3-bromophenyl)carbamate [31] 14=Cipriploxacine(1-cyclopropyl-6-fluoro-4-oxo-7-piperazine-1-ylquinoline-3carboxylic acid) [32] 15 = 2-(Bromomethyl)quinolone [33] 16 = 2-(Trifluoromethyl)quinolone [34] 17= N4-(7-Chloro-4-quinolinyl)-N1,N1-dimethyl-1,4-pentanediamine [35] 18= 8-Hydroxyquinoline [36] 19=Flumequine (7-fluoro-12-methyl-4-oxo-1-azatricyclo[7.3.1.0] [5,13] trideca-2,5,7,9(13)-tetraene-3-carboxylic acid) [37]…”

“…[10] On the other hand, some studies suggest that ribosomal S6 p90 kinase (RSK 1-4), which belongs to the group of highly conserved Ser/Thr kinases, [11] has been related to an increase in prostate cancer. For example, a study showed the Inhibition of RSK and YB-1 (Y-box; regulates androgen receptor expression) [12,13] signaling enhances the anti-cancer effect of enzalutamide in prostate cancer. [14] In addition, a report showed that S6 PMD-026 drug acts as an inhibitor of RSK in combination with enzalutamide in castration-resistant prostate cancer patients.…”

Dynamic Structure-based Pharmacophore Models for Virtual Screening of Small Molecule Libraries Targeting the YB-1

“…12 In the nucleus, YB-1 acts as a transcription and splicing factor, modulating the expression of its target genes. 13 YB-1 has been implicated in various physiological and pathological processes, including cell proliferation, fatty acid synthesis, antifibrotic effects, and cancer progression. 3,[13][14][15] Additionally, YB-1 has been found to interact with other proteins, such as Elongin BC and transportin 1, which can affect its stability, assembly of protein complexes, and subcellular localization.…”

“…13 YB-1 has been implicated in various physiological and pathological processes, including cell proliferation, fatty acid synthesis, antifibrotic effects, and cancer progression. 3,[13][14][15] Additionally, YB-1 has been found to interact with other proteins, such as Elongin BC and transportin 1, which can affect its stability, assembly of protein complexes, and subcellular localization. 16,17 Overall, YB-1 is a multifunctional protein that plays a critical role in various cellular processes and has implications in disease development and progression.…”