Proliferation Of Squamous Cell Carcinoma Research Articles

RIG-I promotes cell proliferation in esophageal squamous cell carcinoma by facilitating p21 degradation.

Retinoic acid-inducible gene-I (RIG-I) is considered a key sensor for host recognition of RNA virus infections. Recent studies have shown that RIG-I also regulates carcinogenesis. However, the role of RIG-I in esophageal squamous cell carcinoma (ESCC) remains unclear. We investigated the RIG-I expression in ESCC cells using a public database, immunohistochemistry, and Western blotting. We evaluated the proliferative activity of ESCC cells using CCK-8, colony formation, and EdU staining assays. Further, we determined the ESCC cell-cycle changes using flow cytometry and the ubiquitination of p21 in the cells using cycloheximide chase and ubiquitination assays. Finally, we verified the in vivo effects of RIG-I on ESCC cells by constructing xenograft models. RIG-I was highly expressed in ESCC cells and significantly promoted their proliferation and cell-cycle. Moreover, RIG-I knockdown inhibited xenograft growth in nude mice. Furthermore, RIG-I accelerated the cell-cycle by promoting the ubiquitination and degradation of p21. Overall, this study revealed that the increased expression of RIG-I due to ESCC accelerated the progression of esophageal cancer by promoting the ubiquitination and degradation of p21, which is related to the prognosis of ESCC. Thus, RIG-I may be a novel therapeutic target for ESCC treatment.

Dihydroorotate dehydrogenase promotes cell proliferation and suppresses cell death in esophageal squamous cell carcinoma and colorectal carcinoma.

Ferroptosis is defined as an iron-dependent non-apoptotic form of programmed cell death. Dihydroorotate dehydrogenase (DHODH) is a newly discovered anti-ferroptosis molecule independent from the well-known GPX4 and AIFM2. However, the expression pattern and especially the functional roles of DHODH during cancer cell death are generally unknown. The databases of Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier Plotter, and Tumor Immune Estimation Resource (TIMER), and methods of colony formation, Cell Counting Kit-8 (CCK-8), adenosine triphosphate (ATP) detection, RNA-seq, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and western blotting were used to analyze the expression level, prognostic role, and oncogenic roles of DHODH in cancers. DHODH overexpression was identified in many types of cancers including esophageal carcinoma (ESCA), colon adenocarcinoma (COAD), rectum adenocarcinoma (READ), and so on. Silence and inactivation of DHODH decreased the abilities of cell proliferation, colony formation, and cellular ATP levels both in esophageal squamous cell carcinoma (ESCC) and colorectal cancer (CRC) cells. Z-VAD-FMK (an apoptosis inhibitor) partially rescued blockade of DHODH-induced death of ESCC cells, and ferroptosis inhibitors (ferrostatin-1 and liproxstatin-1) together with the necroptosis inhibitor (necrostatin-1) partially rescued inhibition of DHODH-induced death of CRC cells, respectively. Pathways including rheumatoid arthritis, salmonella infection, cytokine-cytokine receptor interaction, pertussis, and nuclear factor-κB (NF-κB) were enriched in DHODH-silenced ESCC cells. Overexpression of DHODH augments cell proliferation and suppresses cell death in ESCC and CRC, and DHODH might be developed as a potential anticancer target.

FOXM1a Isoform of Oncogene FOXM1 Is a Tumor Suppressor Suppressed by hnRNP C in Oral Squamous Cell Carcinoma.

FOXM1 is an oncogenic transcriptional factor and includes several isoforms generated by alternative splicing. Inclusion of alternative exon 9 produces FOXM1a, a transcriptionally inactive isoform. However, the role of FOXM1a in tumorigenesis remains unknown. In addition, the regulatory mechanisms of exon 9 splicing are also unclear. In the present study, we found that overexpression of FOXM1a significantly reduced cell proliferation and colony formation of oral squamous cell carcinoma (OSCC) cell proliferation in vitro. Importantly, OSCC cells with FOXM1a overexpression showed significantly slower tumor formation in nude mice. Moreover, we identified a U-rich exonic splicing suppressor (ESS) which is responsible for exon 9 skipping. Splicing factor heterogeneous nuclear ribonucleoprotein C (hnRNP C) can bind to the ESS and suppress exon 9 inclusion and FOXM1a expression. Silence of hnRNP C also significantly suppresses OSCC cell proliferation. HnRNP C is significantly co-expressed with FOXM1 in cancers. Our study uncovered a novel regulatory mechanism of oncogene FOXM1 expression in OSCC.

Epinodosin suppresses the proliferation, invasion, and migration of esophageal squamous cell carcinoma by mediating miRNA-143-3p/Bcl-2 axis.

Epinodosin has shown antibacterial and antitumor biological characteristics in the documents. We found that Epinodosin has an effective inhibitory effect on esophageal squamous cell carcinoma (ESCC). However, the potential roles and mechanisms of Epinodosin in ESCC remain unclear. We performed many experiments to clarify the effect and mechanism of Epinodosin on ESCC. In this study, cell viability, invasion, migration, and apoptosis were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,-diphenytetrazoliumromide (MTT), Transwell, and flow cytometry. The differentially expressed miRNAs were screened through RNA transcriptome sequencing. The expression levels of miRNA-143-3p and some proteins were measured by real-time polymerase chain reaction (PCR) and Western blot. The anticancer effects of Epinodosin in vivo were determined by a nude mouse model. Epinodosin suppressed cell proliferation/invasion/migration and induced ESCC cell apoptosis. Epinodosin remarkably affected the protein expression of mitogen-activated protein kinase (MAPK) signaling pathway. The animal experiments demonstrated that Epinodosin could attenuate the growth of ESCC tumors in nude mice. The expression of p53, Bim, and Bax was upregulated, while that of Bcl-2 was downregulated in tumor tissues. In conclusion, Epinodosin suppresses cell viability/invasion/migration, while induces ESCC cell apoptosis by mediating miRNA-143-3p and Bcl-2, and can markedly attenuate the growth of ESCC tumors in nude mice.

MicroRNA-1271-5p suppresses the proliferation, invasion and migration of oral squamous cell carcinoma by inhibiting F13A1 expression

MicroRNA-1271-5p suppresses the proliferation, invasion and migration of oral squamous cell carcinoma by inhibiting F13A1 expression

Retracted: circCNN2 Accelerates Cell Proliferation and Invasion in Lung Squamous Cell Carcinoma via Regulating miR-184/E2F1 and Activating MAPK Signaling Pathway.

[This retracts the article DOI: 10.1155/2022/6329097.].

Specific knockout of Notch2 in Treg cells significantly inhibits the growth and proliferation of head and neck squamous cell carcinoma in mice

ObjectiveTo investigate the effect of Notch2 gene knockout in Treg cells on head and neck squamous cell carcinoma (HNSCC) in mice. MethodsA mouse model of HNSCC was constructed. Flow cytometry and immunofluorescence were used to examine the numbers of related immune cells and programmed cell death in tumor cells in the spleen and tumor microenvironment of mice. Western blotting was used to measure the expression of related proteins in tumor tissues. ResultsThe tumor volume of regulatory T (Treg) cell-specific Notch2-knockout mice (experimental group) was significantly smaller than that of control mice (control group) (P < 0.05). Compared with those in the control group, the number of Treg cells and the expression of Ki67 in Treg cells in the spleen and tumor tissue were significantly decreased in the experimental group, while the numbers of CD45+ hematopoietic cells, CD4+ T cells, CD8+ T cells, T helper 1 (Th1) cells, CD11b+ cells (macrophages), and CD11b+CD11c+ cells (dendritic cells) and the expression of Ki67 in CD4+ T cells and CD8+ T cells were significantly increased (P < 0.05). There was no significant difference in the number of Th2 cells between the two groups (P > 0.05). Immunofluorescence analysis showed that the numbers of CD4+ T cells and CD8+ T cells in the tumor tissue in the experimental group were significantly higher than those in the control group (P < 0.05). Compared with that in the control group, programmed cell death in the experimental group was significantly increased (P < 0.05). Moreover, the expression levels of NLRP3, Caspase-1 and GSDMD in the tumor tissues of the experimental group were higher than those in the control group (P < 0.01), while the expression levels of BCL2, Bax, ATG5, LC3 and p62 were not significantly different (P > 0.05). ConclusionsSpecific knockout of the Notch2 gene in Treg cells significantly decreases the function of Treg cells, inhibits the growth of HNSCC and improves the immune microenvironment in mice, thus effectively treating HNSCC.

Molecular subtyping and prognostic risk characterization of head and neck squamous cell carcinoma based on lysosome-related genes.

Lysosomes possess a multitude of biological functions and are known to play a crucial role in the proliferation and metastasis of head and neck squamous cell carcinoma (HNSCC). This study aims to systematically investigate the potential role of lysosomes-related genes (LRGs) in the development of heterogeneity and prognosis in HNSCC. Publicly available transcriptome and clinical data of HNSCC were obtained and analyzed using consensus clustering to identify molecular subtypes. A risk model based on LRGs was developed and evaluated, including its correlation with clinical features, immune infiltration, drug sensitivity, and response to immune therapy. Gene set enrichment analysis was conducted to explore relevant pathways, and a prognostic nomogram model for HNSCC was constructed and evaluated. In this study, we identified 542 LRGs that exhibited differential expression in HNSCC, with 116 of these being significantly associated with overall survival. Two LRGs-derived molecular subtypes were identified, which displayed significant differences in prognosis and immune cell infiltration. Additionally, a prognostic risk model was developed, which included 13 LRGs. This model successfully divided HNSCC into low-risk and high-risk groups with different prognoses and immune cell infiltrations. The LRGs-derived risk signature was associated with immune infiltration, clinical features, drug sensitivity and immunotherapy response. The good prognosis of the low-risk group was linked to the activation of immune response-related processes and the inhibition of pathways such as necroptosis and neutrophil extracellular trap formation. Patients in the low-risk group had better immune therapy response, while those in the high-risk group had higher drug sensitivity. Finally, our nomogram, which combines clinical N staging and LRG-derived model, demonstrated excellent prognostic evaluation performance as shown by decision curve analysis and calibration curve. The study provides a comprehensive analysis of the expression and prognostic significance of LRGs in HNSCC, leading to the identification of 2 distinct molecular subtypes and the development of a risk model based on LRGs.

Inhibition of VEGFR2 and EGFR signaling cooperatively suppresses the proliferation of oral squamous cell carcinoma.

Epidermal growth factor receptor (EGFR) is frequently overexpressed in oral squamous cell carcinoma (OSCC), and EGFR-targeting therapeutics have been widely employed to treat patients with a variety of carcinomas including OSCC. Here, we aimed to investigate alternative signaling for OSCC survival under the disruption of EGFR signaling. OSCC cell lines, namely HSC-3 and SAS, were utilized to investigate how EGFR disruption affects cell proliferation. Gene set enrichment analysis was performed to examine how EGFR disruption affects oncogenic signaling in OSCC cells. Disruption of KDR gene was performed using CRISPR/Cas9 techniques. A VEGFR inhibitor, vatalanib was used to research the impact of VEGFR inhibition on OSCC survival. EGFR disruption significantly decreased the proliferation and oncogenic signaling including Myc and PI3K-Akt, in OSCC cells. Chemical library screening assays revealed that VEGFR inhibitors continued to inhibit the proliferation of EGFR-deficient OSCC cells. In addition, CRISPR-mediated disruption of KDR/VEGFR2 retarded OSCC cell proliferation. Furthermore, combined erlotinib-vatalanib treatment exhibited a more potent anti-proliferative effect on OSCC cells, compared to either monotherapy. The combined therapy effectively suppressed the phosphorylation levels of Akt but not p44/42. VEGFR-mediated signaling would be an alternative signaling pathway for the survival of OSCC cells under the disruption of EGFR signaling. These results highlight the clinical application of VEGFR inhibitors in the development of multi-molecular-targeted therapeutics against OSCC.

Linc01614 Regulates the Proliferation, Apoptosis, and Chemotherapy Resistance in Esophageal Squamous Cell Carcinoma by Targeting Mir-4775.

Esophageal squamous cell carcinoma (ESCC), a widely known esophageal disease, severely affects people's health. Numerous investigations demonstrated that long non-coding RNAs (lncRNAs) performed key jobs inside a wide scope of organic cycles and stand out in malignant growth. Our study planned to investigate the roles and mechanisms of linc01614 in ESCC. A Total of 60 ESCC tissue samples including 30 patients with cisplatin sensitivity and 30 patients with cisplatin resistance, who received DDP-based treatment, were obtained from Zhuhai People's Hospital, Zhuhai City during 2021. These tissues were frozen and saved in a -80 °C ultra-low temperature freezer. We performed CCK-8, clone formation, flow cytometry assays to determine the effect of linc01614 on ESCC progression, and explored the specific mechanism of linc01614 in ESCC cell proliferation, apoptosis, and chemotherapy resistance. linc01614 expression was upregulated in ESCC tissues and cells compared with non-tumor tissues and human normal esophageal epithelial cells (Het-1A). Knockdown of linc01614 repressed cell expansion, chemotherapy opposition, and advanced cell apoptosis in ESCC. Besides, linc01614 regulated the expression of miR-4775 as a competitive endogenous RNA (ceRNA). The linc01614/miR-4775 axis played an important role in ESCC progression and drug resistance, revealing that linc01614 is a promising target in ESCC treatment.

Cancer-associated fibroblasts in the invasive tumour front promote the metastasis of oral squamous cell carcinoma through MFAP5 upregulation

Cancer-associated fibroblasts (CAFs) are widely involved in the development and progression of tumours. As a direct junction between tumour and normal host tissue, the invasive tumour front can remodel host tissue to generate a microenvironment more suitable for tumour invasion. However, whether CAFs derived from the invasive front (CAFs-F) have a greater ability to promote tumour invasion than CAFs derived from the superficial tumour (CAFs-S) is unclear. In this study, we characterized primary CAFs from different spatial locations of tumours. We demonstrated that CAFs-F had an increased ability to promote oral squamous cell carcinoma (OSCC) proliferation and invasion in vitro and significantly enhanced tumour growth in vivo compared to CAFs-S. Mechanistically, transcriptome profiling analysis revealed that the expression of MFAP5, encoding microfibril associated protein 5, was dramatically increased in CAFs-F compared to CAFs-S, which further confirmed that the MFAP5 protein level was elevated in head and neck squamous cell carcinoma (HNSCC) and that this increase was correlated with poor survival. Genetic ablation of MFAP5 impaired the preinvasive capabilities of CAFs-F. Together, our findings demonstrated that CAFs-F had a greater ability to promote tumour invasion than CAFs-S and that MFAP5 might be involved in this process.

HMGB1-mediated-TLR4/MyD88 signaling regulates cell proliferation, migration and invasion in esophageal squamous cell carcinoma

Purpose: To study the effect of high mobility group box protein 1 (HMGB1)-mediated toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) on esophageal squamous cell carcinoma (ESCC). &#x0D; Methods: Cell viability was determined using CCK-8 test and colony formation assay, while cell migration and invasion were assessed by Transwell assay. Western blotting was used to determine protein and mRNA expression levels. The effect of TLR4/MyD88 signaling pathway on proliferation of ESCC cells was investigated via in vitro knockdown of HMGB1. &#x0D; Results: Data from in vitro experiments indicated that HMGB1 knockdown significantly decreased the proliferation, migration, and invasion of EC9706 cells in siHMGB1 group, when compared with siNC group (number of invasive cells in siHMGB1 vs. corresponding number in siNC: 26.7 ± 4.5 vs. 68.7 ± 2.5; p &lt; 0.01), and also decreased proliferation, migration and invasion of TE-9 cells in siHMB1, relative to siNC group (number of invasive cells in siHMGB1 vs. corresponding number in siNC: 29.3 ± 3.5 vs. 55.7 ± 3.1; p &lt; 0.01). Moreover, MGB1 knockdown via siTLR4 transfection significantly down-regulated the expressions of TLR4/MyD88 and epithelial-mesenchymal transition (EMT), but over-expression of TLR4 reversed the inhibition by HMGB1 knockdown on ESCC cells (p &lt; 0.01). &#x0D; Conclusion: These findings suggest that HMGB1-mediated TLR4/MyD88 signal pathway is a potential treatment route for ESCC.

FBXW7 promotes autophagy and inhibits proliferation of oral squamous cell carcinoma.

F-box and WD repeat domain containing 7 (FBXW7) is a critical tumor suppressor. The expression of FBXW7 is decreased in oral squamous cell carcinoma (OSCC) tissues and shows diagnosis value. We aimed to investigate the influence of FBXW7 overexpression on OSCC cell proliferation and autophagy. In Balb/c nude mice, CAL27 xenograft tumor model was established. Western blot was employed to evaluate protein level. Messenger RNA level was analyzed by quantitative reverse transcription-polymerase chain reaction. Colony formation assay and MTT assay were employed to evaluate cell proliferation. FBXW7 expression was decreased in OSCC cell lines. FBXW7 inhibited cell proliferation of SCC9 and CAL27. FBXW7 increased Autophagy related 7 (Atg7), Beclin1 (BECN1), B-cell lymphoma 2 (BCL2) -associated X (BAX), BCL2 antagonist killer (BAK), and microtubule-associated protein 1 light chain 3 (LC3) levels and decreased MCL1 and BCL2 levels in CAL27 cells. FBXW7 decreased tumor volume and weight in CAL27 xenograft tumor model. FBXW7 increased BECN1, Atg7, and LC3 levels in CAL27 xenograft tumor model. In conclusion, decreased expression of FBXW7 is confirmed in diverse OSCC cell lines. The enhanced FBXW7 expression inhibits cancer cell proliferation and promotes autophagy in both OSCC cells and xenograft tumor model.

Long noncoding RNA TUG1 promotes proliferation, migration and cisplatin resistance in oral squamous cell carcinoma.

Long noncoding RNA TUG1 promotes proliferation, migration and cisplatin resistance in oral squamous cell carcinoma.

"Pharyngolaringeal Neoplasm Treated with Surgery and Radiotherapy – Squamous Cell Carcinoma with Sarcomatoid Dedifferentiation – Clinical Case"

"Sarcomatoid carcinoma is a rare and aggressive form of squamous cell carcinoma (SCC). It is a biphasic tumor that has been shown to be a dedifferentiated monoclonal form of classic squamous cell carcinoma. The factors that contribute to proliferation of SCC to sarcomatoid carcinoma are not precisely known but some studies revealed the importance of anterior radiation therapy. This case report describes a 62-year-old man, heavy smoker and alcohol drinker diagnosed with laryngeal neoplasm. The pathological diagnosis was well-differentiated SCC of the piriform sinus. Surgery was performed and the pathology report revealed medium differentiated SCC, pT4aN1M0. The patient underwent external radiotherapy (RT) with 66Gy/tumour bed in 33 fractions. At 4 months post RT the clinical exam revealed tumor recurrence near the tracheal stoma. A second surgery was performed and the pathology diagnosed a recurrence of SCC with sarcomatoid-looking areas, with two surgical margins being invaded by the tumor. Postoperative computer tomography (CT) of the neck showed no evidence of macroscopic disease. The next treatment used was chemotherapy with 4 cycles of carboplatin paclitaxel but soon after, an inoperable locoregional recurrence was diagnosed and he started treatment with Nivolumab followed by rapid locoregional progression. Squamous cell carcinoma with sarcomatoid dedifferentiation is a rare histology of laryngeal cancer, with an aggressive behavior that requires intense treatment and follow-up."

239 The expression of RGR and correlation with proliferation and aberrant differentiation in cutaneous squamous cell carcinomas

239 The expression of RGR and correlation with proliferation and aberrant differentiation in cutaneous squamous cell carcinomas

Sterol regulatory element binding transcription factor 1 promotes proliferation and migration in head and neck squamous cell carcinoma.

Sterol-regulatory element-binding protein 1 (SREBP1) is a transcription factor involved in lipid metabolism that is encoded by sterol regulatory element binding transcription factor 1(SREBF1). SREBP1 overexpression is associated with the progression of several human tumors; however, the role of SREBP1 in head and neck squamous cell carcinoma (HNSC) remains unclear. SREBF1 expression in pan-cancer was analyzed using the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data, and the association between SREBF1 expression and clinical characteristics of HNSC patients was examined using the UALCAN database. Enrichment analysis of SREBF1-related genes was performed using the Cluster Profiler R package. TCGA database was used to investigate the relationship between immune cell infiltration and SREBF1 expression. CCK-8, flow cytometry, and wound healing assays were performed to investigate the effect of SREBF1 knockdown on the proliferation and migration of HNSC cells. SREBF1 was significantly upregulated in several tumor tissues, including HNSC, and SREBF1 overexpression was positively correlated with sample type, cancer stage, tumor grade, and lymph node stage in HNSC patients. Gene enrichment analysis revealed that SREBF1 is associated with DNA replication and homologous recombination. SREBF1 upregulation was positively correlated with the infiltration of cytotoxic cells, B cells, T cells, T helper cells, and NK CD56 bright cells in HNSC. Knockdown of SREBF1 inhibited the proliferation and migration of HNSC cells (Hep2 and TU212) and induced apoptosis by downregulating the expression of steroidogenic acute regulatory protein-related lipid transfer 4 (STARD4). SREBF1 may promote HNSC proliferation, migration and inhibit apoptosis by upregulating STARD4 and affecting the level of immune cell infiltration.

Downregulation of microRNA‑494 inhibits cell proliferation in lung squamous cell carcinoma via the induction of PUMA‑α‑mediated apoptosis.

Increased evidence has shown that abnormal microRNA (miRNA) plays pivotal roles in numerous types of cancer. However, their expression, function and mechanism in lung squamous cell carcinoma (LSCC) remains to be fully elucidated. The aim of the present study was to investigate the suppressive role of miR-494 in LSCC progression and elucidate its regulatory mechanism. By analyzing expression profiles of miRNAs in LSCC tissues using miRNA microarray, it was revealed that miR-494 was significantly upregulated in 22 pairs of LSCC tissues. Subsequently, reverse transcription-quantitative PCR was performed to determine the expression of miR-494 and p53-upregulated-modulator-of-apoptosis-α (PUMA-α). Western blot analysis was conducted to examine protein levels. Dual-luciferase reporter assay was used to confirm the binding between miR-494 and PUMA-α. Annexin V-fluoresceine isothiocyanate/propidium iodide staining and CCK-8 assays were employed to determine cell apoptosis and cell viability, respectively. It was also revealed that miR-494 was highly expressed in LSCC cell lines compared with that in 16HBE cells. Further experiments confirmed that knockdown of miR-494 reduced cell viability and induced LSCC apoptosis. Bioinformatics analysis predicted that miR-494 could potentially target PUMA-α; also known as Bcl-2-binding component 3, a pro-apoptotic factor, and an inverse correlation between the expression of miR-494 and PUMA-α mRNA levels in LSCC tissues was found. Furthermore, PUMA-α inhibition could reverse the promoting effect of miR-494 knockdown on apoptosis in LSCC cells. Taken together, these findings demonstrated that miR-494 functions as an oncogene by targeting PUMA-α in LSCC, and miR-494 may serve as a novel therapeutic target for treating LSCC.

Tumor-Derived CCL5 Recruits Cancer-Associated Fibroblasts and Promotes Tumor Cell Proliferation in Esophageal Squamous Cell Carcinoma.

These data highlight the role of CCL5 in tumorigenesis and the therapeutic potential of targeting the CCL5-CCR5 axis in ESCC.

Abstract 400: TIP60-mediated regulation of DNp63a is associated with cisplatin resistance

Abstract About 5.4 million basal and squamous cell skin cancers are diagnosed each year in the US. The chemotherapeutic drug, Cisplatin is often used to treat squamous cell carcinoma (SCC) patients, but low response rates and disease recurrence is common. ΔNp63α, a member of the p53 family of transcription factors, is overexpressed and considered oncogenic in non-melanoma skin cancer where it regulates cell survival, promotes proliferation and inhibits cell apoptosis. ΔNp63α has also been shown to promote resistance to cisplatin by transcriptionally regulating several DNA damage response (DDR) genes. A previous study from our lab showed that the histone acetyltransferase (HAT) TIP60 promotes SCC proliferation by positively regulating ΔNp63α protein levels in manner dependent on the catalytic activity of TIP60. This finding suggested that TIP60 may contribute to the failure of platinum-based drugs in SCC and led us to hypothesize that TIP60-mediated acetylation of ΔNp63α regulates its stability and transcriptional activity to promote chemoresistance. Silencing endogenous TIP60 led to a decrease in ΔNp63α transcript and protein levels in multiple SCC cell lines, indicating the positive regulation of ΔNp63α by TIP60 is not cell-line specific. Further, TIP60 levels positively correlated with ΔNp63α stability, protein levels and cisplatin resistance. Stable expression of TIP60 or ΔNp63α individually promoted resistance to cisplatin and reduced cell death, whereas loss of ΔNp63α and TIP60 induced G2/M arrest, increased cell-death and sensitized cells to cisplatin. Moreover, pharmacological inhibition of TIP60 reduced acetylation of ΔNp63α and sensitized resistant cells to cisplatin. Finally, we demonstrated that ΔNp63α and TIP60 levels positively correlated with DNA repair capacity and negatively correlated with cisplatin-DNA adduct formation. Silencing of either TIP60 or ΔNp63α enhanced cisplatin-DNA adduct formation and significantly reduced expression of genes involved in DDR. Taken together, our data indicate that TIP60-mediated stabilization of ΔNp63α increases cisplatin resistance and provides critical insights into the mechanisms by which ΔNp63α confers cisplatin resistance through regulation of genes involved in DNA damage repair. Our findings suggest that inhibition of TIP60 may be therapeutically advantageous in overcoming cisplatin resistance in SCC other epithelial cancers. Citation Format: Akshay Hira, Andrew J. Stacy, Jin Zhang, Mike Kemp, Madhavi P. Kadakia. TIP60-mediated regulation of DNp63a is associated with cisplatin resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 400.