Journal: International Journal of Molecular Sciences

Article Title: Expression and Clinical Significance of MAPK8 , MAPK9 , MAP2K4 , and MAP2K7 Genes in Colorectal Cancer

doi: 10.3390/ijms27010100

Figure Lengend Snippet: Comparison of MAP2K7, MAPK9, and MAPK8 gene expression and histological grade of CRC. * multiplication sign.

Article Snippet: Assay IDs for molecular probes: Hs00387426_m1—MAP2K4; Hs01547883_g1—MAP2K7; Hs01548508_m1—MAPK8; Hs01558224_m1—MAPK9; Hs02786624_g1—GAPDH; and Hs01060665_g1—ACTB.

Techniques: Comparison, Gene Expression

Journal: International Journal of Molecular Sciences

Article Title: Expression and Clinical Significance of MAPK8 , MAPK9 , MAP2K4 , and MAP2K7 Genes in Colorectal Cancer

doi: 10.3390/ijms27010100

Figure Lengend Snippet: Comparison of MAP2K7 gene expression and primary tumor size.

Article Snippet: Assay IDs for molecular probes: Hs00387426_m1—MAP2K4; Hs01547883_g1—MAP2K7; Hs01548508_m1—MAPK8; Hs01558224_m1—MAPK9; Hs02786624_g1—GAPDH; and Hs01060665_g1—ACTB.

Techniques: Comparison, Gene Expression

Journal: International Journal of Molecular Sciences

Article Title: Expression and Clinical Significance of MAPK8 , MAPK9 , MAP2K4 , and MAP2K7 Genes in Colorectal Cancer

doi: 10.3390/ijms27010100

Figure Lengend Snippet: Comparison of MAPK8 , MAP2K7 , and MAP2K4 gene expression between colon tumor tissue and normal colon tissue.

Article Snippet: Assay IDs for molecular probes: Hs00387426_m1—MAP2K4; Hs01547883_g1—MAP2K7; Hs01548508_m1—MAPK8; Hs01558224_m1—MAPK9; Hs02786624_g1—GAPDH; and Hs01060665_g1—ACTB.

Techniques: Comparison, Gene Expression

Journal: International Journal of Molecular Sciences

Article Title: Expression and Clinical Significance of MAPK8 , MAPK9 , MAP2K4 , and MAP2K7 Genes in Colorectal Cancer

doi: 10.3390/ijms27010100

Figure Lengend Snippet: Comparison of MAPK8 , MAP2K4 , and MAP2K7 gene expression with various clinicopathological features.

Article Snippet: Assay IDs for molecular probes: Hs00387426_m1—MAP2K4; Hs01547883_g1—MAP2K7; Hs01548508_m1—MAPK8; Hs01558224_m1—MAPK9; Hs02786624_g1—GAPDH; and Hs01060665_g1—ACTB.

Techniques: Comparison, Gene Expression

Journal: International Journal of Molecular Sciences

Article Title: Expression and Clinical Significance of MAPK8 , MAPK9 , MAP2K4 , and MAP2K7 Genes in Colorectal Cancer

doi: 10.3390/ijms27010100

Figure Lengend Snippet: Kaplan–Meier curves representing the survival rate of patients with colorectal cancer in relation to MAPK8 , MAPK9 , MAP2K4 , and MAP2K7 expression.

Article Snippet: Assay IDs for molecular probes: Hs00387426_m1—MAP2K4; Hs01547883_g1—MAP2K7; Hs01548508_m1—MAPK8; Hs01558224_m1—MAPK9; Hs02786624_g1—GAPDH; and Hs01060665_g1—ACTB.

Techniques: Expressing

Journal: International Journal of Molecular Sciences

Article Title: Expression and Clinical Significance of MAPK8 , MAPK9 , MAP2K4 , and MAP2K7 Genes in Colorectal Cancer

doi: 10.3390/ijms27010100

Figure Lengend Snippet: Differences in the expression of MAPK8, MAPK9, MAP2K4, and MAP2K7 genes in colorectal cancer tissue according to CMS. p -values were calculated using one-way ANOVA.

Article Snippet: Assay IDs for molecular probes: Hs00387426_m1—MAP2K4; Hs01547883_g1—MAP2K7; Hs01548508_m1—MAPK8; Hs01558224_m1—MAPK9; Hs02786624_g1—GAPDH; and Hs01060665_g1—ACTB.

Techniques: Expressing

Journal: Chinese Herbal Medicines

Article Title: Ganoderic acid a derivative induces apoptosis of cervical cancer cells by inhibiting JNK pathway

doi: 10.1016/j.chmed.2024.07.002

Figure Lengend Snippet: (A) Target prediction analysis results. (B) Prediction of GaAD19-JNK interaction. (C–E) Western blot analysis of HeLa cells with GaAD19 treatment for 24 h on expression of JNK, p-JNK, ERK, p-ERK, p38, p-p38 (C), AMPK α 1, p-AMPK α 1-S485, p-AMPK α 1-S496, AMPK β 1, p-AMPK β 1-S108, Akt, p-Akt (D), MAP2K4, MAP2K7 (E), and other proteins (means ± SD, n = 3). (F) Effect of GaAD19 on mRNA level of JNK pathway membrane protein receptor in HeLa cells was determined by qPCR (means ± SD, n = 3). ( ** P < 0.01, *** P < 0.001 vs control group, ns indicates no significant difference).

Article Snippet: MAP2K7 , Proteintech , 55030–1-AP , 1:500.

Techniques: Western Blot, Expressing, Membrane, Control

Journal: Journal of Experimental & Clinical Cancer Research : CR

Article Title: JNK pathway suppression mediates insensitivity to combination endocrine therapy and CDK4/6 inhibition in ER+ breast cancer

doi: 10.1186/s13046-025-03466-9

Figure Lengend Snippet: MAP2K7 loss leads to reduced JNK phosphorylation and diminished induction of JNK-induced stress response. (A) Representative Western blot of MKK7, MKK4 and GAPDH in MCF-7 pLenti and MAP2K7 −/− (MKK7_1 and MKK7_3) cells (full length blots in Supplementary Fig. B). (B) Quantitation of MKK7 expression by densitometry. Band intensity normalised to GAPDH. Data analysed by one-way ANOVA with Tukey’s multiple comparisons test. (C) Representative Western blot of MKK7, MKK4 and GAPDH in T-47D pLenti and MAP2K7 −/− (MKK7_1 and MKK7_3) cells (full length blots in Supplementary Fig. D). (D) Quantitation of MKK7 expression by densitometry. Band intensity normalised to GAPDH. Data analysed by one-way ANOVA with Tukey’s multiple comparisons test. (E) Metastases to lung of MCF-7 pLenti and MKK7_3 xenografts ( n = 10 mice per arm) as measured by cytokeratin immunohistochemistry. Number of metastases (mets) quantitated per 1 × 10 7 µm area and analysed by unpaired two-tailed t-test. Representative images shown, scale bar = 200 μm. (F) Representative Western blot of pJNK T183/Y185 , JNK and GAPDH in MCF-7 pLenti and MAP2K7 −/− (MKK7_1 and MKK7_3) cells (full length blots in Supplementary Fig. F). (G) Quantitation of pJNK T183/Y185 activity by densitometry. Band intensity normalised to GAPDH. Data analysed by one-way ANOVA with Tukey’s multiple comparisons test. (H) Representative Western blot of pJNK T183/Y185 , JNK and GAPDH in T-47D pLenti and MAP2K7 −/− (MKK7_1 and MKK7_3) cells (full length blots in Supplementary Fig. H). (I) Quantitation of pJNK T183/Y185 activity by densitometry. Band intensity normalised to GAPDH. Data analysed by one-way ANOVA with Tukey’s multiple comparisons test. (J) Expression of pJNK T183/Y185 in primary ER+ breast cancers from the TCGA cohort compared to MAP2K7 copy number status. MAP2K7 “no loss” ( n = 478) includes cancers with amplified, gain or diploid status for MAP2K7 . MAP2K7 “loss” ( n = 138) includes cancers with heterozygous or homozygous deletion of MAP2K7 . Data analysed by unpaired two-tailed t-test. (K) Representative Western blot of pJNK T183/Y185 , JNK and GAPDH in MCF-7 pLenti and MAP2K7 −/− (MKK7_1 and MKK7_3) cells treated with 300 nM anisomycin for 0, 30, 60, 90 min (full length blots in Supplementary Fig. I). (L) Quantitation of pJNK T183/Y185 activity by densitometry. Band intensity normalised to GAPDH. Data analysed by two-way ANOVA with Tukey’s multiple comparisons test. (M) Representative Western blot of pJNK T183/Y185 , JNK and GAPDH in T-47D pLenti and MAP2K7 −/− (MKK7_1 and MKK7_3) cells treated with 300 nM anisomycin for 0, 30, 60, 90 min (full length blots in Supplementary Fig. K). (N) Quantitation of pJNK T183/Y185 activity by densitometry. Band intensity normalised to GAPDH. Data analysed by two-way ANOVA with mixed effects analysis and Tukey’s multiple comparisons test. (O) Representative Western blot of pJNK T183/Y185 , JNK2 (detected by JNK antibody), JNK1 and GAPDH in CRISPR/Cas9 MCF-7 cell lines: pLenti, MAPK8 −/− and MAPK9 −/− . Cells were treated with 300 nM anisomycin for 0, 30, 60, 90 min (full length blots in Supplementary Fig. M). (P-Q) JNK1 (P) and JNK2 (Q) expression quantitated at 0 min timepoint. Band intensity normalised to GAPDH. Data analysed by one-way ANOVA with Tukey’s multiple comparisons test. (R) Quantitation of pJNK T183/Y185 activity by densitometry. Band intensity normalised to GAPDH. Data analysed by two-way ANOVA with Tukey’s multiple comparisons test. (S-T) Expression of pJNK T183/Y185 in primary ER+ breast cancers from the TCGA cohort compared to MAPK8 (S) or MAPK9 (T) copy number status. MAPK8 ( n = 488) or MAPK9 ( n = 545) “no loss” includes cancers with amplified, gain or diploid status for MAPK8 or MAPK9 . MAPK8 ( n = 384) or MAPK9 ( n = 379) “loss” includes cancers with heterozygous or homozygous deletion of MAPK8 or MAPK9 . Data analysed by unpaired two-tailed t-test

Article Snippet: MAP2K7 (hs00178198_m1), JUN (hs01103582_s1), JUND (hs04187679_s1), ATF3 (hs00231069_m1) and RPLP0 (hs_00420895_gh) Taqman probes (Thermo Fisher Scientific) were used to analyse mRNA expression levels using a QuantStudio7 Flex Real-Time PCR System.

Techniques: Phospho-proteomics, Western Blot, Quantitation Assay, Expressing, Immunohistochemistry, Two Tailed Test, Activity Assay, Amplification, CRISPR

Journal: Journal of Experimental & Clinical Cancer Research : CR

Article Title: JNK pathway suppression mediates insensitivity to combination endocrine therapy and CDK4/6 inhibition in ER+ breast cancer

doi: 10.1186/s13046-025-03466-9

Figure Lengend Snippet: MAP2K7 loss prevents growth arrest and senescence induction following endocrine therapy + CDK4/6 inhibitor treatment (A) Representative Western blot of ERα, MKK7, pJNK T183/Y185 , JNK and GAPDH in MCF-7 pLenti and MAP2K7 −/− (MKK7_1 and MKK7_3) cells treated with 500 nM tamoxifen + 250 nM palbociclib (tam + palb), 25 nM fulvestrant + 125 nM palbociclib (fas + palb) or vehicle (Absolute ethanol (EtOH) and tetrahydrofuran (THF)) for 48 h (full length blots in Supplementary Fig. D). (B) Quantitation of MKK7 expression by densitometry. Band intensity normalised to GAPDH. Data analysed by two-way ANOVA with Tukey’s multiple comparisons test. (C) Quantitation of pJNK T183/Y185 activity by densitometry. Band intensity normalised to GAPDH. Data analysed by two-way ANOVA with Tukey’s multiple comparisons test. (D) Representative Western blot of ERα, MKK7, pJNK T183/Y185 , JNK and GAPDH in T-47D pLenti and MAP2K7 −/− (MKK7_1 and MKK7_3) cells treated with 500 nM tamoxifen + 250 nM palbociclib (tam + palb), 25 nM fulvestrant + 125 nM palbociclib (fas + palb) or vehicle (EtOH and THF) for 48 h (full length blots in Supplementary Fig. F). (E) Quantitation of MKK7 expression by densitometry. Band intensity normalised to GAPDH. Data analysed by two-way ANOVA with Tukey’s multiple comparisons test. (F) Quantitation of pJNK T183/Y185 activity by densitometry. Band intensity normalised to GAPDH. Data analysed by two-way ANOVA with Tukey’s multiple comparisons test. (G) MCF-7 pLenti and MAP2K7 −/− (MKK7_1 and MKK7_3) cells treated with 500 nM tamoxifen + 250 nM palbociclib (tam + palb), 25 nM fulvestrant + 125 nM palbociclib (fas + palb) or vehicle (EtOH and THF) and analysed by time-lapse microscopy using an IncuCyte ZOOM over 7 days. Cell count determined by red fluorescent count, and data analysed by two-way ANOVA with Sidak’s multiple comparisons test. Experiment performed in quadruplicate. (H) T-47D pLenti and MAP2K7 −/− (MKK7_1 and MKK7_3) cells treated with 500 nM tamoxifen + 250 nM palbociclib (tam + palb), 25 nM fulvestrant + 125 nM palbociclib (fas + palb) or vehicle (EtOH and THF) and analysed by time-lapse microscopy using an IncuCyte ZOOM over 7 days. Cell count determined by red fluorescent count, and data analysed by two-way ANOVA with Sidak’s multiple comparisons test. Experiment performed in triplicate. (I) Representative colony formation from MCF-7 pLenti and MAP2K7 −/− (MKK7_1 and MKK7_3) cells treated with 500 nM tamoxifen + 250 nM palbociclib (tam + palb), 25 nM fulvestrant + 125 nM palbociclib (fas + palb) or vehicle (EtOH and THF) for 3 weeks, with colony formation detected with 0.1–0.5% crystal violet stain. (J) Colony formation quantitated using ImageJ. Data analysed by two-way ANOVA with Tukey’s multiple comparisons test. (K) Representative brightfield images of MCF-7 pLenti and MAP2K7 −/− (MKK7_1 and MKK7_3) cells treated with 500 nM tamoxifen + 250 nM palbociclib (tam + palb), 25 nM fulvestrant + 125 nM palbociclib (fas + palb) or vehicle (EtOH and THF) for 72 h and stained with senescence-associated β-galactosidase. (L) Quantification of MCF-7 pLenti and MAP2K7 −/− cells staining positive for senescence-associated β-galactosidase from (K) . Data analysed by two-way ANOVA with Tukey’s multiple comparisons test. Scale bar = 100 μm. (M) Representative brightfield images of T-47D pLenti and MAP2K7 −/− (MKK7_1 and MKK7_3) cells treated with 500 nM tamoxifen + 250 nM palbociclib (tam + palb), 25 nM fulvestrant + 125 nM palbociclib (fas + palb) or vehicle (EtOH and THF) for 72 h and stained with senescence-associated β-galactosidase. (N) Quantification of T-47D pLenti and MAP2K7 −/− cells staining positive for senescence-associated β-galactosidase from (M) . Data analysed by two-way ANOVA with Tukey’s multiple comparisons test. Scale bar = 100 μm

Article Snippet: MAP2K7 (hs00178198_m1), JUN (hs01103582_s1), JUND (hs04187679_s1), ATF3 (hs00231069_m1) and RPLP0 (hs_00420895_gh) Taqman probes (Thermo Fisher Scientific) were used to analyse mRNA expression levels using a QuantStudio7 Flex Real-Time PCR System.

Techniques: Western Blot, Quantitation Assay, Expressing, Activity Assay, Time-lapse Microscopy, Cell Counting, Staining

Journal: Journal of Experimental & Clinical Cancer Research : CR

Article Title: JNK pathway suppression mediates insensitivity to combination endocrine therapy and CDK4/6 inhibition in ER+ breast cancer

doi: 10.1186/s13046-025-03466-9

Figure Lengend Snippet: MAP2K7 loss alters the transcriptional response to endocrine therapy + CDK4/6 inhibitor treatment (A) Experimental schematic of pLenti and MKK7_3 cells (MCF-7 or T-47D) treated with 500 nM tamoxifen + 250 nM palbociclib (tam + palb), 25 nM fulvestrant + 125 nM palbociclib (fas + palb) or vehicle (Absolute ethanol (EtOH) and tetrahydrofuran (THF)) for 48 h. RNA collected and analysed by RNAseq. (B) Multidimensional scale analysis of RNAseq data of MCF-7 cells +/- treatments, and T-47D cells +/- treatments. (C) Relative change in gene expression between vehicle and treatment (tamoxifen + palbociclib or fulvestrant + palbociclib) of MAP2K7 −/− vs. pLenti cells. Boxed regions are genes that are less downregulated, or less upregulated, in MKK7_3 cells compared to pLenti cells. Pearson’s correlation coefficient shown. (D) Analysis of gene set enrichment of hallmark gene sets from genes that show attenuated downregulation (purple dots) or upregulation (orange dots) with treatment in MAP2K7 −/− cells, in either MCF-7 or T-47D cell lines. Size of dot is fold enrichment of the signature, with enriched signatures with false discovery rate (FDR) of 0.05. FDR values listed in Supplementary Table . (E) Venn spider plots of transcription factors (TFs) commonly deregulated in MAP2K7 −/− MCF-7 and MAP2K7 −/− T-47D cells that are untreated; veh = vehicle; boxed region contains significantly altered TFs. (F) Venn spider plots of TFs commonly deregulated in MAP2K7 −/− MCF-7 and T-47D cells that are treated with combination therapy; tam + palb = 500 nM tamoxifen + 250 nM palbociclib; or fas + palb = 25 nM fulvestrant + 125 nM palbociclib; boxed region contains significantly altered TFs

Article Snippet: MAP2K7 (hs00178198_m1), JUN (hs01103582_s1), JUND (hs04187679_s1), ATF3 (hs00231069_m1) and RPLP0 (hs_00420895_gh) Taqman probes (Thermo Fisher Scientific) were used to analyse mRNA expression levels using a QuantStudio7 Flex Real-Time PCR System.

Techniques: Gene Expression

Journal: Journal of Experimental & Clinical Cancer Research : CR

Article Title: JNK pathway suppression mediates insensitivity to combination endocrine therapy and CDK4/6 inhibition in ER+ breast cancer

doi: 10.1186/s13046-025-03466-9

Figure Lengend Snippet: Depletion of JNK signalling in ER+ breast cancer, and in endocrine therapy/palbociclib resistance (A) JNK1, pJNK1 Y185 ( NP_001265477.1 ), JNK2, pJNK2 Y185 ( NP_001128516.1 ) Clinical Proteomic Tumour Analysis Consortium data from the TCGA cohort, showing expression in normal breast tissue ( n = 18) and luminal breast cancers ( n = 64). Data analysed by unpaired two-tailed t-test. (B) Copy number status of MAP3K11 , MAP2K4 , MAP2K7 , MAPK8 , MAPK9 , JUN and ESR1 in primary (TCGA; n = 808 and METABRIC; n = 1817) and metastatic (Metastatic Breast Cancer Project; n = 77) cohorts. Data analysed by unpaired two-tailed t-test. (C) Kaplan-Meier curves of the probability of overall survival and progression-free survival in ER+ breast cancers comparing high, medium, and low tertiles of JNK pathway expression, where JNK pathway is MAP2K7 , MAPK8 and MAPK9 . Kaplan-Meier analysis performed on pooled breast cancer datasets using KMPlotter . P-value calculated by Log-rank (Mantel-Cox) test. (D) Correlation of JNK pathway with the anti-proliferative response of pre-operative palbociclib (POP) trial ER+ breast cancer patients . Anti-proliferative response determined by change in TYMS mRNA expression between initial biopsy and post-treatment (∆ TYMS ) and correlated with JNK signalling ( MAP2K7 , MAPK8 and MAPK9 ). Pearson’s correlation coefficient shown. (E) Immunohistochemistry analysis of advanced metastatic ER+ breast cancer cohort treated with endocrine therapy + CDK4/6 inhibition. Images of FFPE sections with high, medium, and low pJNK T183/Y185 activity. Scale bar = 100 μm. (F) Kaplan-Meier curves of survival in the endocrine + CDK4/6 inhibitor-treated cohort comparing tertiles of low, medium and high pJNK T183/Y185 expression. Significance determined by Log-rank (Mantel-Cox) test. (G) mRNA expression of MAP3K11 , MAP2K4 , MAP2K7 , MAPK8 , MAPK9 and JUN stratified into patients who did not develop metastatic disease (no metastasis; n = 107) and patients who did (metastasis; n = 48). Comparisons between metastatic and non-metastatic by Mann-Whitney unpaired two-tailed t-test. (H) Anti-proliferative response of POP trial ER+ breast cancer patients and association with individual JNK pathway genes. Patients with high ( n = 64) and low ( n = 8) JNK pathway gene expression ( MAP3K11 , MAP2K4 , MAP2K7 , MAPK8 , MAPK9 and JUN ) were stratified based on TYMS anti-proliferative response. Comparisons between high and low by unpaired two-tailed t-test

Article Snippet: MAP2K7 (hs00178198_m1), JUN (hs01103582_s1), JUND (hs04187679_s1), ATF3 (hs00231069_m1) and RPLP0 (hs_00420895_gh) Taqman probes (Thermo Fisher Scientific) were used to analyse mRNA expression levels using a QuantStudio7 Flex Real-Time PCR System.

Techniques: Expressing, Two Tailed Test, Immunohistochemistry, Inhibition, Activity Assay, MANN-WHITNEY, Gene Expression