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ITGB4 positively correlated with enfortumab vedotin target <t>NECTIN4.</t> A , the RNA-Seq analysis in the GSE268855 dataset after overexpressing ITGB4 ; B , the correlation analysis in the DepMap dataset. p values are shown in the figure. C , Pan-cancer data analysis in the DepMap database revealed the correlation between ITGB4 and NECTIN4 . p values were shown in the figure. D – G , HT-1376 and 5637 cells were transfected with shITGB4 or shControl for 72 h. The harvested cells were used for Western blot analysis ( D ) and RT-qPCR detection ( E – G ). H – K , HT-1376 and 5637 cells were transfected with overexpressed ITGB4 plasmid or empty vector for 72 h, and harvested cells were used for Western blot analysis ( H ) and RT-qPCR detection ( I–K ). Data presents as mean ± SD with three replicates. ns, not significant; ∗, p < 0.05; ∗∗, p < 0.01; ∗∗∗, p < 0.001. L , the tissue microarray of bladder cancer stained with ITGB4 and NECTIN4, respectively. The typical IHC images stained with ITGB4 and NECTIN4 are shown in the panel . M , the correlation of these two proteins is shown in the panel , and the p -value is indicated in the figure.
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ITGB4 positively correlated with enfortumab vedotin target NECTIN4. A , the RNA-Seq analysis in the GSE268855 dataset after overexpressing ITGB4 ; B , the correlation analysis in the DepMap dataset. p values are shown in the figure. C , Pan-cancer data analysis in the DepMap database revealed the correlation between ITGB4 and NECTIN4 . p values were shown in the figure. D – G , HT-1376 and 5637 cells were transfected with shITGB4 or shControl for 72 h. The harvested cells were used for Western blot analysis ( D ) and RT-qPCR detection ( E – G ). H – K , HT-1376 and 5637 cells were transfected with overexpressed ITGB4 plasmid or empty vector for 72 h, and harvested cells were used for Western blot analysis ( H ) and RT-qPCR detection ( I–K ). Data presents as mean ± SD with three replicates. ns, not significant; ∗, p < 0.05; ∗∗, p < 0.01; ∗∗∗, p < 0.001. L , the tissue microarray of bladder cancer stained with ITGB4 and NECTIN4, respectively. The typical IHC images stained with ITGB4 and NECTIN4 are shown in the panel . M , the correlation of these two proteins is shown in the panel , and the p -value is indicated in the figure.

Journal: The Journal of Biological Chemistry

Article Title: Integrin β4 drives immune evasion and therapeutic resistance to PD-1 blockade in bladder cancer via MEK/ERK signaling

doi: 10.1016/j.jbc.2025.110941

Figure Lengend Snippet: ITGB4 positively correlated with enfortumab vedotin target NECTIN4. A , the RNA-Seq analysis in the GSE268855 dataset after overexpressing ITGB4 ; B , the correlation analysis in the DepMap dataset. p values are shown in the figure. C , Pan-cancer data analysis in the DepMap database revealed the correlation between ITGB4 and NECTIN4 . p values were shown in the figure. D – G , HT-1376 and 5637 cells were transfected with shITGB4 or shControl for 72 h. The harvested cells were used for Western blot analysis ( D ) and RT-qPCR detection ( E – G ). H – K , HT-1376 and 5637 cells were transfected with overexpressed ITGB4 plasmid or empty vector for 72 h, and harvested cells were used for Western blot analysis ( H ) and RT-qPCR detection ( I–K ). Data presents as mean ± SD with three replicates. ns, not significant; ∗, p < 0.05; ∗∗, p < 0.01; ∗∗∗, p < 0.001. L , the tissue microarray of bladder cancer stained with ITGB4 and NECTIN4, respectively. The typical IHC images stained with ITGB4 and NECTIN4 are shown in the panel . M , the correlation of these two proteins is shown in the panel , and the p -value is indicated in the figure.

Article Snippet: The primary antibodies used were as follows: ITGB4 (#21738-1-AP, Proteintech, 1:500 dilution), p-ITGB4(Y1510) (#YP0755, Immunoway, 1:500 dilution), MEK-1(#YM8273, Immunoway, 1:1000 dilution), p-MEK-1 (T386) (#YP0425, Immunoway, 1:500 dilution), ERK1/2(#YM8336, Immunoway, 1:2000 dilution), p-ERK1/2 (T202/T204) (#YM8452, Immunoway, 1:2000 dilution), c-Jun (#YM8321, Immunoway, 1:2000 dilution), p-c-Jun (S63) (#28907-1-AP, Proteintech, 1:500 dilution), PD-L1(#28076-1-AP, Proteintech, 1:300 dilution), NECTIN4 (#21903-1-AP, Proteintech, 1:2000 dilution), HER2(#18299-1-AP, Proteintech, 1:2000 dilution), TROP2(#27360-1-AP, Proteintech, 1:500 dilution), GADPH (#10494-1-AP, Proteintech, 1:5000 dilution).

Techniques: RNA Sequencing, Transfection, Western Blot, Quantitative RT-PCR, Plasmid Preparation, Microarray, Staining

ITGB4 plays a vital role in BLCA sequential therapies. A mechanism diagram depicting that the highly expressed ITGB4 in cisplatin-resistant BLCA activated the MEK/ERK pathway through tyrosine-1510 phosphorylation, upregulated the expression level of PD-L1 in BLCA, and caused anti-PD-1 treatment resistance. Meanwhile, the overexpressed ITGB4 was positively correlated to NECTIN4, promoting the sensitivity of BLCA to enfortumab vedotin treatment.

Journal: The Journal of Biological Chemistry

Article Title: Integrin β4 drives immune evasion and therapeutic resistance to PD-1 blockade in bladder cancer via MEK/ERK signaling

doi: 10.1016/j.jbc.2025.110941

Figure Lengend Snippet: ITGB4 plays a vital role in BLCA sequential therapies. A mechanism diagram depicting that the highly expressed ITGB4 in cisplatin-resistant BLCA activated the MEK/ERK pathway through tyrosine-1510 phosphorylation, upregulated the expression level of PD-L1 in BLCA, and caused anti-PD-1 treatment resistance. Meanwhile, the overexpressed ITGB4 was positively correlated to NECTIN4, promoting the sensitivity of BLCA to enfortumab vedotin treatment.

Article Snippet: The primary antibodies used were as follows: ITGB4 (#21738-1-AP, Proteintech, 1:500 dilution), p-ITGB4(Y1510) (#YP0755, Immunoway, 1:500 dilution), MEK-1(#YM8273, Immunoway, 1:1000 dilution), p-MEK-1 (T386) (#YP0425, Immunoway, 1:500 dilution), ERK1/2(#YM8336, Immunoway, 1:2000 dilution), p-ERK1/2 (T202/T204) (#YM8452, Immunoway, 1:2000 dilution), c-Jun (#YM8321, Immunoway, 1:2000 dilution), p-c-Jun (S63) (#28907-1-AP, Proteintech, 1:500 dilution), PD-L1(#28076-1-AP, Proteintech, 1:300 dilution), NECTIN4 (#21903-1-AP, Proteintech, 1:2000 dilution), HER2(#18299-1-AP, Proteintech, 1:2000 dilution), TROP2(#27360-1-AP, Proteintech, 1:500 dilution), GADPH (#10494-1-AP, Proteintech, 1:5000 dilution).

Techniques: Phospho-proteomics, Expressing