Journal: EMBO Molecular Medicine

Article Title: Targeting pre-existing club-like cells in prostate cancer potentiates androgen deprivation therapy

doi: 10.1038/s44321-026-00375-y

Figure Lengend Snippet: ( A , B ) Expression per Pten pc−/− LSC med cell subpopulation ( A ) and UMAP projection ( B ) of Pim1 . ( C , D ) Number ( C ) and size ( D ) of organoids generated from sorted Pten pc−/− LSC med cells after 10 days of culture in medium containing DMSO or 1 nM JQ-1 and 1 nM CX-6258, alone or combined, as indicated. Data were normalized to the control (DMSO) condition (biological replicates, n = 5 independent experiments). ** p < 0.01; *** p < 0.001; **** p < 0.0001 (one-way ANOVA and Dunnett post hoc test). Exact p values are reported in Appendix Table . ( E , F ) Enrichment of various epithelial cell signatures ( E ) and LSC med subpopulation signatures ( F ) in HPV-10, PC-3, DU145, LNCaP, and 22Rv1 cell lines (Data Ref: Wang et al, ). ( G ) Enrichment of CRPC-AR, CRPC-WNT, CRPC-NE, and CRPC-SCL human tumoral subtypes signatures (Dataset ) in HPV-10, PC-3, DU145, LNCaP, and 22Rv1 cell lines. ( H ) Human HPV-10 cells were treated for 72 h with 1 µM JQ-1 and 1 µM CX-6258, alone or combined (as indicated), then the number of adherent cells was counted (biological replicates, n = 4 independent experiments). The data were normalized to the control condition (DMSO). ** p < 0.01; *** p < 0.001 (one-way ANOVA and Dunnett post hoc test). Exact p values are reported in Appendix Table . ( I ) Images of HPV-10 cells after 72 h of treatment. ( J ) The viability of HPV-10 cells (adherent + in suspension) was determined by trypan blue staining (biological replicates, n = 4 independent experiments). ns not significant; * p < 0.05 (one-way ANOVA and Dunnett post hoc test). Exact p values are reported in Appendix Table . ( K , L ) Same as ( H , J ) with PC-3 cells (biological replicates, n = 4 independent experiments). ns not significant; * p < 0.05, ** p < 0.01; *** p < 0.001 (one-way ANOVA and Dunnett post hoc test). Exact p values are reported in Appendix Table . ( M ) Tumorsphere-forming capacity of HPV-10 cells in medium containing DMSO or 1 µM JQ-1 and 1 µM CX - 6258, alone or combined as indicated. Data were normalized to the DMSO condition (biological replicates, n = 3 independent experiments). *** p < 0.001 (one-way ANOVA and Dunnett post hoc test). Exact p values are reported in Appendix Table . All error bars in this figure represent SD. .

Article Snippet: HPV-10 , ATCC , CRL-2220 RRID: CVCL_3495.

Techniques: Expressing, Generated, Control, Suspension, Staining

Journal: EMBO Molecular Medicine

Article Title: Targeting pre-existing club-like cells in prostate cancer potentiates androgen deprivation therapy

doi: 10.1038/s44321-026-00375-y

Figure Lengend Snippet: ( A , B ) Dose-response of JQ-1 ( A ) and CX-6258 ( B ) on the number of organoids formed by sorted Pten pc−/− LSC med cells. Data are normalized to the DMSO condition (biological replicates, n = 5 ( A ) and n = 4 ( B ) independent experiments). **** p < 0.0001 versus DMSO (ANOVA analysis and Dunnett’s post hoc test). Exact p values are reported in Appendix Table . ( C ) Expression of FOSL1 and PIM1 in human HPV-10 cells determined by RT-qPCR. The results are normalized to the values obtained in LNCaP cells, represented by the horizontal dotted line (biological replicates, n = 3 independent experiments). * p < 0.05 versus LNCaP cells (unpaired t -test with Welch’s correction), p = 0.0157 ( FOSL1 ), p = 0.0278 ( PIM1 ). ( D ) Dose-response of JQ-1 and CX-6258 on the number of adherent HPV-10 cells. Data were normalized to the DMSO condition (each dot is the average of three biological replicates). **** p < 0.0001 versus DMSO (ordinary two-way ANOVA with Šídák multiple comparisons test). Exact p values are reported in Appendix Table . ( E – H ) Human PC-3 ( E , F ) and HPV-10 ( G , H ) cells were treated with T5224-PROTAC (‘PROTAC’) at 0, 8, and 24 h. The cells were collected at 48 h. The cell number ( E , G ) and cell viability (adherent + in suspension) ( F , H ) were determined by trypan blue staining (biological replicates, n = 4 independent experiments). The data were normalized to DMSO (control condition). * p < 0.05, ** p < 0.01 (ANOVA analysis and Dunn’s post hoc test). ( I ) Human PC-3 cells were treated with siRNA (siScrambled or three different FOSL1 siRNA, as indicated) for 6 h and the cells were collected at 48 h. The expression of FOSL1 was measured by RT-qPCR (biological replicates, n = 2 independent experiments). The data were normalized to siScrambled (control condition). The three siRNA FOSL1 showed similar efficacy. **** p < 0.0001 (ANOVA analysis and Dunnett’s post hoc test). Exact p values are reported in Appendix Table . ( J – L ) Human PC-3 cells were treated with siScrambled or siFOSL1(1) for 6 h and the cells were collected at 72 h. Cell number ( J ) and cell viability (adherent + in suspension) ( K ) were determined by trypan blue staining. The expression of FOSL1 ( L ) was measured by RT-qPCR. The data are normalized to siScrambled (biological replicates, n = 3 independent experiments). ** p < 0.01, *** p < 0.001, **** p < 0.0001 (two-tailed t -test). Exact p values are reported in Appendix Table . All error bars in this figure represent SD.

Article Snippet: HPV-10 , ATCC , CRL-2220 RRID: CVCL_3495.

Techniques: Expressing, Quantitative RT-PCR, Suspension, Staining, Control, Two Tailed Test

Journal: bioRxiv

Article Title: L-type channel voltage-dependent facilitation results from asymmetric π-H and π-π quadrangle interactions at DI–DII domains

doi: 10.64898/2026.01.23.701029

Figure Lengend Snippet: (A) Structural representation of DI–DII PD interface in Ca V 2.1-WT and Ca V 2.1-T698F mutant. Possible π-H and π-π quadrangle interaction in Ca V 2.1-T698F mutant shown as dotted lines. (B) Aligned amino acid sequences of DIIS6, DIIP2, and DIP1 PD helices from human (h) and mouse (m) L-type (Ca V 1.1–1.4) and Ca V 2 (2.1–2.3) channels. Conserved and unique residues participating in π-H and π-π quadrangle interactions are highlighted. (C) Representative whole-cell current traces of Ca V 2.1-WT, Ca V 2.1-T698F, and Ca V 1.2-F737T mutants coexpressed with β 1 b in tsA-201 cells before (P1) or after (P2) DPP to 100 mV. Voltage protocol is represented in dotted box above. (D) Mean fitted plots of Ca V 2.1-WT, Ca V 2.1-T698F, and Ca V 1.2-F737T mutants in response to DPP ranging from 0 to 180 mV. Cell numbers are represented in brackets. (E) Bar plots display the maximum VDF at 120 mV DPP for Ca V 2.1-WT, Ca V 2.1-T698F, and Ca V 1.2-F737T mutants. Unpaired Student’s t-test used statistical significance. All plots represent mean ± SEM. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, **p < 0.0001, ns, p > 0.05 (non-significant).

Article Snippet: In experiments involving P/Q-type currents, the cDNA of Ca V 2.1 (α 1A , human, Addgene ID: 140575 ) was co-transfected with β 1 b at a 1:0.75 ratio.

Techniques: Mutagenesis

Journal: bioRxiv

Article Title: L-type channel voltage-dependent facilitation results from asymmetric π-H and π-π quadrangle interactions at DI–DII domains

doi: 10.64898/2026.01.23.701029

Figure Lengend Snippet: (A) Aligned amino acid sequences of DIIS6, DIIP2, and DIP1 PD helices from rat (r) and rabbit (rb) L-type (Ca V 1.1–1.4) and Ca V 2 (2.1–2.3) channels. Conserved and unique residues participating in the π-H and π-π quadrangle interactions are highlighted. (B and C) Representative whole-cell current traces (top) with Current density (pA/pF) and normalized conductance (G/G max ) vs. voltage plots (below) of WT or mutants of Ca V 1.2/Ca V 2.1 channels. Voltage protocol is represented in dotted box above. Insets display half-maximal activation voltages. (D and E) Normalized current traces (left) of WT and mutant Ca V 1.2/Ca V 2.1 channels at 0 mV showing channel inactivation. Time constant of inactivation (τ) plots (right) from exponential fits of 0 mV traces. All plots represent mean ± SEM (cell numbers in brackets). Unpaired Student’s t-test used for statistical significance. *p ≤ 0.05, **p ≤ 0.01, ns, non-significant.

Article Snippet: In experiments involving P/Q-type currents, the cDNA of Ca V 2.1 (α 1A , human, Addgene ID: 140575 ) was co-transfected with β 1 b at a 1:0.75 ratio.

Techniques: Activation Assay, Mutagenesis