biostudies-literatureHira AU.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)NCI NIH HHS877https://www.ebi.ac.uk/biostudies/studies/S-EPMC11615348biostudies-literatureUnknown15(12)Non-melanoma skin cancer, including basal and squamous cell carcinoma, is the most common form of cancer worldwide, with approximately 5.4 million new cases diagnosed each year in the United States. While the chemotherapeutic drug cisplatin is often used to treat squamous cell carcinoma (SCC) patients, low response rates and disease recurrence are common. In this study, we show that TIP60 and ΔNp63α levels correlate with cisplatin resistance in SCC cell lines, suggesting that TIP60 contributes to the failure of platinum-based drugs in SCC by regulating the stability and transcriptional activity of ΔNp63α. Depletion of endogenous TIP60 or pharmacological inhibition of TIP60 led to a decrease in ΔNp63α protein and acetylation levels in multiple SCC cell lines. We showed that TIP60 upregulateCell death & diseaseTIP60 enhances cisplatin resistance via regulating ΔNp63α acetylation in SCC.PMC116153481R01CA280075R01 CA280075Zhang JHira AKadakia MPfalseTIP60 enhances cisplatin resistance via regulating ΔNp63α acetylation in SCC.Non-melanoma skin cancer, including basal and squamous cell carcinoma, is the most common form of cancer worldwide, with approximately 5.4 million new cases diagnosed each year in the United States. While the chemotherapeutic drug cisplatin is often used to treat squamous cell carcinoma (SCC) patients, low response rates and disease recurrence are common. In this study, we show that TIP60 and ΔNp63α levels correlate with cisplatin resistance in SCC cell lines, suggesting that TIP60 contributes to the failure of platinum-based drugs in SCC by regulating the stability and transcriptional activity of ΔNp63α. Depletion of endogenous TIP60 or pharmacological inhibition of TIP60 led to a decrease in ΔNp63α protein and acetylation levels in multiple SCC cell lines. We showed that TIP60 upregulate2024-01-01T00:00:00Z2024 Dec2025-04-18T12:54:54.706Z2025-04-04T01:14:56.949ZS-EPMC116153483962718610.1038/s41419-024-07265-6