Journal: Frontiers in Oncology

Article Title: CFTR functions as a tumor suppressor in adenoid cystic carcinoma and its silencing reveals an associated vulnerability involving the Hsp70 chaperone system

doi: 10.3389/fonc.2026.1836263

Figure Lengend Snippet: Pharmacological modulation of Hsp70 alters cell viability and reveals divergent MAPK1 transcriptional responses in SACC-83 and SACC-LM cells. (A) Cell viability of SACC-83 and SACC-LM cells treated with VER155008 at 0, 10, 20, and 40 μM, as determined by CCK-8 assay. (B) Positive cell ratio of SACC-83 and SACC-LM cells treated with HSF1A at 0, 200, 500, 1000, and 1500 nM, as determined by CCK-8 assay. (C) RT-qPCR analysis of MAPK1 and HSPA1A mRNA expression in SACC-83 cells following VER155008 treatment (left, middle) and HSPA1A expression following HSF1A treatment (right). (D) RT-qPCR analysis of MAPK1 and HSPA1A mRNA expression in SACC-LM cells following VER155008 treatment (left, middle) and HSPA1A expression following HSF1A treatment (right). (E) Representative Western blot images showing Hsp70 protein expression in SACC-83 cells treated with VER155008 or HSF1A, with GAPDH as the loading control. (F) Densitometric quantification of Hsp70 protein levels normalized to GAPDH in SACC-83 cells following VER155008 (left) and HSF1A (right) treatment. (G) Representative Western blot images showing Hsp70 protein expression in SACC-LM cells treated with VER155008 or HSF1A, with GAPDH as the loading control. (H) Densitometric quantification of Hsp70 protein levels normalized to GAPDH in SACC-LM cells following VER155008 (left) and HSF1A (right) treatment. Data are presented as mean ± SD from n = 3 independent biological experiments. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.

Article Snippet: The functional impact of Hsp70 modulation was assessed using the inhibitor VER155008 (MedChemExpress, HY10941) and the heat shock response activator HSF1A (MedChemExpress, HY103000 ).

Techniques: CCK-8 Assay, Quantitative RT-PCR, Expressing, Western Blot, Control

Journal: Frontiers in Oncology

Article Title: CFTR functions as a tumor suppressor in adenoid cystic carcinoma and its silencing reveals an associated vulnerability involving the Hsp70 chaperone system

doi: 10.3389/fonc.2026.1836263

Figure Lengend Snippet: Pharmacological modulation of Hsp70 alters the migration and invasion capacities of SACC-83 and SACC-LM cells. (A, B) Wound-healing assays evaluating the migration of SACC-83 (A) and SACC-LM (B) cells following VER155008 treatment. (C, D) Wound-healing assays evaluating the migration of SACC-83 (C) and SACC-LM (D) cells following HSF1A treatment. (E, F) Transwell invasion assays assessing the invasive capacity of SACC-83 (E) and SACC-LM (F) cells treated with VER155008. (G, H) Transwell invasion assays assessing the invasive capacity of SACC-83 (G) and SACC-LM (H) cells treated with HSF1A. Data are presented as mean ± SD from n = 3 independent biological experiments. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.

Article Snippet: The functional impact of Hsp70 modulation was assessed using the inhibitor VER155008 (MedChemExpress, HY10941) and the heat shock response activator HSF1A (MedChemExpress, HY103000 ).

Techniques: Migration

Journal: Frontiers in Oncology

Article Title: CFTR functions as a tumor suppressor in adenoid cystic carcinoma and its silencing reveals an associated vulnerability involving the Hsp70 chaperone system

doi: 10.3389/fonc.2026.1836263

Figure Lengend Snippet: Pharmacological and genetic modulation of Hsp70 modulates the proliferation and apoptosis of SACC-83 and SACC-LM cells. (A, B) CCK-8 assays evaluating the proliferation of SACC-83 cells following VER155008 (A) or HSF1A (B) treatment. (C, D) CCK-8 assays evaluating the proliferation of SACC-83 cells with Hsp70 knockdown (C) or overexpression (D) combined with VER155008 treatment. (E, F) CCK-8 assays evaluating the proliferation of SACC-LM cells following VER155008 (E) or HSF1A (F) treatment. (G, H) CCK-8 assays evaluating the proliferation of SACC-LM cells with Hsp70 knockdown (G) or overexpression (H) combined with VER155008 treatment. (I, J) Flow cytometry analysis of apoptosis in SACC-83 cells treated with VER155008 (I) or HSF1A (J) . (K, L) Flow cytometry analysis of apoptosis in SACC-LM cells treated with VER155008 (K) or HSF1A (L) . Data are presented as mean ± SD from n = 3 independent biological experiments. *P < 0.05, ****P < 0.0001.

Article Snippet: The functional impact of Hsp70 modulation was assessed using the inhibitor VER155008 (MedChemExpress, HY10941) and the heat shock response activator HSF1A (MedChemExpress, HY103000 ).

Techniques: CCK-8 Assay, Knockdown, Over Expression, Flow Cytometry

Journal: bioRxiv

Article Title: NFYA regulates two sequential genome-wide transcriptional activation events during oocyte to embryo transition

doi: 10.64898/2026.03.30.715371

Figure Lengend Snippet: (A) Left upper panel: schematic diagram of the experimental design. Left lower panel: the embryo development rate upon DMSO or G&V treatment (Ganetespib 5nM and VER155008 5μM). The data are presented as mean ± SEM. [DMSO, n = 67; G&V (1C-B), n = 64; G&V (4C-B), n = 47. N represents the total number of embryos from two independent experiments]. Right panel: representative images of blastocyst stage embryos after chaperones inhibition (G&V). Scale bar,100 μm. Red arrows indicate representative arrested embryos in G&V (1C-B) group. (B) Scatter plots comparing gene expression profiles of late-2cell embryos treated with G&V or DMSO. The x and y axis of the dot plots are Log 2 CPM from RNA-seq. Fold change > 2, FDR < 0.05. ZGA genes, n=2,773. (C) Venn diagram showing the overlapped downregulated ZGA genes between NFYA depleted (NFYA-dTAG) and G&V treated L2C embryos. P values (Fisher’s exact test, two-sided) for overlapped genes are also shown. (D) Upper panel: schematic diagram of the experimental design. Lower left panel: ovarian morphology of 6 days in vitro cultured P4 ovaries with DMSO and G&V treatment. DDX4 stained oocytes. The white arrowhead indicates representative growing oocytes. Scale bar, 50 μm. Lower right panel: numbers of growing oocytes (DDX4 positive oocytes bigger than 25 μm in diameter that were surrounded by cuboidal granulosa cells) in each ovary after 6 days culture with DMSO and G&V treatment. Quantitative data are shown as mean ± SEM; ∗∗p < 0.01, Student’s t test. (E) Scatter plots comparing the gene expression profiles of growing oocytes (GOs) from 6 days in vitro cultured P4 ovaries with G&V or DMSO. The x and y axis of the dot plots are Log 2 CPM from RNA-seq. Fold change > 2, FDR < 0.05. PFA genes, n=2,463. (F) Venn diagram showing the overlapped downregulated PFA genes between Nfy a-cKO and G&V treated GOs. P values (Fisher’s exact test, two-sided) for overlapped genes are also shown. (G) Model illustrating the role of NFYA in PFA and ZGA. Before PFA (primordial), the PFA genes are silenced. Subsequently (primary and secondary), NFYA binding promotes open chromatin and activates PFA genes through promoter and distal binding. Loss of NFYA leads to reduced chromatin accessibility, defective PFA, and early follicular degeneration. Before ZGA (1C), the ZGA genes are silenced. Subsequently (L2C), NFYA activates ZGA genes through promoter and enhancer binding. Loss of NFYA leads to defective ZGA and predominantly embryo arrest at 2-cell stage. (H) NFYA pre-occupies and regulates a set of genes, including chaperones and histone genes, common in both PFA and ZGA through conserved promoter binding.

Article Snippet: Ganetespib (MCE, HY-15205) and VER155008 (Selleckchem, S7751) were reconstituted in DMSO to a 100 mM or 150 mM stocks, respectively.

Techniques: Inhibition, Gene Expression, RNA Sequencing, In Vitro, Cell Culture, Staining, Binding Assay

Journal: Translational Oncology

Article Title: Overcoming the leptomeningeal seeding of medulloblastoma by targeting HSP70

doi: 10.1016/j.tranon.2026.102695

Figure Lengend Snippet: Pharmacologic inhibition of HSP70 selectively suppresses viability of seeding cells. (A–F) Dose-response bar graphs showing the effects of six different HSP70 inhibitors on cell viability in non-seeding cells (N3, white bars) and seeding cells (S3, black bars) at the specified concentrations for 72 h. These panels demonstrate that S3 cells exhibit greater sensitivity to HSP70 inhibition compared to N3 cells. (G) Cell viability of S3 cells treated with VER155008 at its IC₅₀ concentration, showing a significant reduction compared to untreated controls. (H) Summary quantification graph of the six HSP70 inhibitors, highlighting relative potency in reducing S3 cell viability. (I) Western blot analysis of HSP70, MRP1, and MRP2 protein expression in S3 cells following VER155008 treatment. β-actin was used as a loading control. Data are shown as mean ± SD from n = 3 independent experiments. Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc test. **P < 0.01, ***P < 0.001.

Article Snippet: VER155008, Apoptozole, HA15, TRC051384, JG98 , Elesclomol, cisplatin (Selleckchem, Houston, TX.

Techniques: Inhibition, Concentration Assay, Western Blot, Expressing, Control

Journal: Translational Oncology

Article Title: Overcoming the leptomeningeal seeding of medulloblastoma by targeting HSP70

doi: 10.1016/j.tranon.2026.102695

Figure Lengend Snippet: In vitro and in vivo evaluation of combination therapy targeting HSP70 in LMS model. (A, E) Dose-response curves for single and combination treatments of VER155008 with cisplatin (A) or 4HC (E) in S3 cells. The leftward shift of the combination curve (pink line) compared to monotherapy (black line) indicates enhanced efficacy. (B, F) Combination Index (CI) vs. fraction affected (Fa) plots for VER155008 + cisplatin combination (B) and VER155008 + 4HC combination (F), generated by CompuSyn software. CI values below 1 indicate synergy. (C, G) Isobologram analysis for VER155008 + cisplatin combination (C) and VER155008 + 4HC combination (G), showing dose pairs required to achieve 50% (Fa = 0.5, blue), 75% (Fa = 0.75, red), and 90% (Fa = 0.9, green) growth inhibition. (D) Cell viability comparison between single-agent and combination treatments of VER155008 with cisplatin in S3 cells. (H) Cell viability comparison between single-agent and combination treatments of VER155008 with 4HC in S3 cells. The combination showed significantly greater inhibitory effect than monotherapy. (I) Representative bioluminescence imaging (BLI) of LMS-bearing mice treated with vehicle, VER155008 alone, or in combination with cisplatin or ifosfamide (IFO) at days 1, 10, and 17. (J) Longitudinal quantification of BLI signal intensity in the brain region of interest (ROI) over time for each treatment group. (K) Longitudinal quantification of BLI signal intensity in the spinal cord region of interest (ROI) over time for each treatment group. Quantification of photon flux was performed for brain and spinal cord regions of interest (ROI) at the indicated time points. In vivo data are presented as mean ± SD, with n = 5 mice per group. Statistical analysis was conducted using repeated-measures ANOVA followed by post hoc testing. *P < 0.05, **P < 0.01, ***P < 0.001.

Article Snippet: VER155008, Apoptozole, HA15, TRC051384, JG98 , Elesclomol, cisplatin (Selleckchem, Houston, TX.

Techniques: In Vitro, In Vivo, Generated, Software, Inhibition, Comparison, Imaging