Translational Oncology最新文献

{"title":"Therapeutic potential of tLyp-1-EV-shCTCF in inhibiting liver cancer stem cell self-renewal and immune escape via SALL3 modulation in hepatocellular carcinoma","authors":"","doi":"10.1016/j.tranon.2024.102048","DOIUrl":"10.1016/j.tranon.2024.102048","url":null,"abstract":"<div><p>The progression of hepatocellular carcinoma (HCC) is influenced by disrupted metabolic processes, presenting challenges in prognostic outcomes. Hepatocellular carcinoma (HCC), a leading cause of cancer-related mortality, is closely associated with metabolic reprogramming and stem cell-like properties in liver cancer stem cells (LCSCs). This study explored the potential molecular mechanisms by which tLyP-1-modified extracellular vesicles (EVs) delivering CTCF shRNA (tLyp-1-EV-shCTCF) regulate mitochondrial DNA methylation-induced glycolytic metabolic reprogramming and LCSC self-renewal. Through a series of methods, including Western blot, nanoparticle tracking analysis, and immunofluorescence, we demonstrated the successful delivery and internalization of tLyp-1-EV in HCC cells. Our results identified SALL3 as a critical factor underexpressed in HCC and LCSCs, while CTCF was overexpressed. Overexpression of SALL3 inhibited LCSC self-renewal and immune evasion by blocking the CTCF-DNMT3A interaction, thus repressing DNMT3A methyltransferase activity and subsequent mitochondrial DNA methylation-mediated glycolytic metabolic reprogramming. <em>In vivo</em> experiments further supported these findings, showing that tLyp-1-EV-shCTCF treatment significantly reduced tumor growth by upregulating SALL3 expression, thereby inhibiting glycolytic metabolic reprogramming and enhancing the immune response against HCC cells. This study provides novel insights into the role of SALL3 and mitochondrial DNA methylation in HCC progression, offering potential therapeutic targets for combating HCC and its stem cell-like properties.</p></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S193652332400175X/pdfft?md5=4becfd946383cbafd804d66a255b79fe&pid=1-s2.0-S193652332400175X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142058370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The immunological landscape and silico analysis of key paraptosis regulator LPAR1 in gastric cancer patients","authors":"","doi":"10.1016/j.tranon.2024.102110","DOIUrl":"10.1016/j.tranon.2024.102110","url":null,"abstract":"<div><p>This study aims to identify key regulators of paraptosis in gastric cancer (GC) and explore their potential in guiding therapeutic strategies, especially in stomach adenocarcinoma (STAD). Genes associated with paraptosis were identified from the references and subjected to Cox regression analysis in the TCGA-STAD cohort. Using machine learning models, LPAR1 consistently ranked highest in feature importance. Multiple sequencing data showed that LPAR1 was significantly overexpressed in cancer-associated fibroblasts (CAFs). LPAR1 expression was significantly higher in normal tissues, and ROC analysis demonstrated its discriminative ability. Copy number alterations and microsatellite instability were significantly associated with LPAR1 expression. High LPAR1 expression correlated with advanced tumor grades and specific cancer immune subtypes, and multivariate analysis confirmed LPAR1 as an independent predictor of poor prognosis. LPAR1 expression was associated with different immune response metrics, including immune effector activation and upregulated chemokine secretion. High LPAR1 expression also correlated with increased sensitivity to compounds, such as BET bromodomain inhibitors I-BET151 and RITA, suggesting LPAR1 as a biomarker for predicting drug activity. FOXP2 showed a strong positive correlation with LPAR1 transcriptional regulation, while increased methylation of LPAR1 promoter regions was negatively correlated with gene expression. Knockdown of LPAR1 affected cell growth in most tumor cell lines, and in <em>vitro</em> experiments demonstrated that LPAR1 influenced extracellular matrix (ECM) contraction and cell viability in the paraptosis of CAFs. These findings suggest that LPAR1 is a critical regulator of paraptosis in GC and a potential biomarker for drug sensitivity and immunotherapy response. This underscores the role of CAFs in mediating tumorigenic effects and suggests that targeting LPAR1 could be a promising strategy for precision medicine in GC.</p></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1936523324002377/pdfft?md5=4b69d1ec237a0405eb8cfb8cdb6240c3&pid=1-s2.0-S1936523324002377-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142049481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional regulation of DLGAP5 by AR suppresses p53 signaling and inhibits CD8+ T cell infiltration in triple-negative breast cancer","authors":"","doi":"10.1016/j.tranon.2024.102081","DOIUrl":"10.1016/j.tranon.2024.102081","url":null,"abstract":"<div><p>Triple-negative breast cancer (TNBC) is a challenging subtype with unclear biological mechanisms. Recently, the transcription factor androgen receptor (AR) and its regulation of the DLGAP5 gene have gained attention in TNBC pathogenesis. In this study, we found a positive correlation between high AR expression and TNBC cell proliferation and growth. Furthermore, we confirmed DLGAP5 as a critical downstream regulator of AR with high expression in TNBC tissues. Knockdown of DLGAP5 significantly inhibited TNBC cell proliferation, migration, and invasion. AR was observed to directly bind to the DLGAP5 promoter, enhancing its transcriptional activity and suppressing the activation of the p53 signaling pathway. <em>In vivo</em> experiments further validated that downregulation of AR or DLGAP5 inhibited tumor growth and enhanced CD8⁺ <em>T</em> cell infiltration. This study highlights the crucial roles of AR and DLGAP5 in TNBC growth and immune cell infiltration. Taken together, AR inhibits the p53 signaling pathway by promoting DLGAP5 expression, thereby impacting CD8⁺ <em>T</em> cell infiltration in TNBC.</p></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1936523324002080/pdfft?md5=0caeea541f8c0ff0adeadb7f7ea2b02a&pid=1-s2.0-S1936523324002080-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combining Mitomycin C with inhibition of BAD phosphorylation enhances apoptotic cell death in advanced cervical cancer","authors":"","doi":"10.1016/j.tranon.2024.102103","DOIUrl":"10.1016/j.tranon.2024.102103","url":null,"abstract":"<div><h3>Objective</h3><p>Mitomycin C (MMC), a DNA-damaging chemotherapeutic, is commonly used clinically for recurrent cervical carcinoma (CC), either alone or in combination. MMC generates DNA damage resulting in CC cell death yet also induces increased AKT-BAD phosphorylation associated with drug resistance and reduced clinical benefit. The present study evaluates the efficacy of combined MMC and a BAD phosphorylation inhibitor in CC.</p></div><div><h3>Methods</h3><p>The association and function of phosphorylation of BAD on serine 99 (pBADS99) for cell survival of both MMC-resistant or sensitive-CC cells was explored. BAD was mutated to BADS99A to examine the requirement of BADS99 for CC cell survival and a novel small-molecule inhibitor of pBADS99 was utilized. Cell proliferation, survival, foci formation, and patient-derived organoids (PDOs) assays were utilized to determine efficacy, synergy and related mechanisms.</p></div><div><h3>Results</h3><p>MMC IC₅₀ was positively correlated to the cell line pBADS99/BAD ratio. Increased BADS99 phosphorylation was observed in both MMC-sensitive or -resistant CC cells after MMC treatment. Inhibition of pBADS99 in CC cell lines produced synergistic apoptosis through BAD-mediated apoptotic pathways and enhanced DNA damage in response to MMC. The concurrent use of pharmacological inhibition of pBADS99 and MMC was synergistic, resulting in diminished cell viability and inducing apoptotic cell death in MMC-sensitive and -resistant CC cell lines or patient-derived organoids.</p></div><div><h3>Conclusion</h3><p>A combination of MMC with inhibition of BAD phosphorylation potentiated efficacy compared to single agent treatment. The potential further development of such strategies may provide outcome benefits to patients with CC.</p></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1936523324002304/pdfft?md5=f1614516e9ababa5ba2278e41e7bfc03&pid=1-s2.0-S1936523324002304-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photoimmunotherapy for cancer treatment based on organic small molecules: Recent strategies and future directions","authors":"","doi":"10.1016/j.tranon.2024.102086","DOIUrl":"10.1016/j.tranon.2024.102086","url":null,"abstract":"<div><p>Photodynamic therapy (PDT) is considered as a promising anticancer approach, owning to its high efficiency and spatiotemporal selectivity. Ample evidence indicated that PDT can trigger immunogenic cell death by releasing antigens that activate immune cells to promote anti-tumor immunity. Nevertheless, the inherent nature of tumors and their complex heterogeneity often limits the efficiency of PDT, which can be overcome with a novel strategy of photo-immunotherapy (PIT) strategy. By exploring the principles of PDT induction and ICD enhancement, combined with other therapies such as chemotherapy or immune checkpoint blockade, the tailored solutions can be designed to address specific challenges of drug resistance, hypoxic conditions, and tumor immunosuppressive microenvironments (TIMEs), which enables targeted enhancement of systemic immunity to address most distant and recurrent cancers. The present article summarizes the specific strategies of PIT and discusses recent existing limitations. More importantly, we anticipate that the perspectives presented herein will help address the clinical translation challenges associated with PIT.</p></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1936523324002134/pdfft?md5=5b1e73366947aecae48c9ea0f362d1a8&pid=1-s2.0-S1936523324002134-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142049438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WDR77 in Pan-Cancer: Revealing expression patterns, genetic insights, and functional roles across diverse tumor types, with a spotlight on colorectal cancer","authors":"","doi":"10.1016/j.tranon.2024.102089","DOIUrl":"10.1016/j.tranon.2024.102089","url":null,"abstract":"<div><h3>Objective</h3><p>Despite its involvement in regulating various cellular functions, the expression and role of WD repeat-containing protein 77 (WDR77) in cancer remain elusive. This study aims to explore the expression and potential roles of WDR77 across multiple cancers, with a particular focus on its relevance in colorectal cancer (CRC).</p></div><div><h3>Methods</h3><p>We obtained WDR77 RNA-seq data, mutations, CNVs, and DNA methylation data from the TCGA, GTEx, and GEO databases to investigate its expression patterns and prognostic value. Additionally, we examined the correlation between WDR77 expression and somatic mutations, copy number variations, DNA methylation, and mRNA modifications. We utilized GSVA, GSEA algorithms, and CRISPR KO data from the Dependency Map database to explore WDR77′s potential biological functions. The association between WDR77 and the tumor immune microenvironment was investigated using ESTIMATE and IOBR algorithms. Finally, we assessed WDR77 expression in CRC and its impact on cell proliferation through qRT-PCR, Western blotting, immunohistochemistry, CCK8, colony formation, and EdU assays.</p></div><div><h3>Results</h3><p>WDR77 was upregulated in various tumors and correlated with poor patient prognosis. Its high expression positively correlated with pathways related to cell proliferation and negatively correlated with immune-related pathways. In CRC, WDR77 expression was associated with specific clinical features, genomic alterations, and immune microenvironment characteristics. Experimental validation confirmed upregulated WDR77 expression in CRC tissues and cells, with WDR77 knockdown significantly inhibiting CRC cell proliferation.</p></div><div><h3>Conclusion</h3><p>WDR77 holds potential as an oncogene and biological marker in various cancers, particularly CRC.</p></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S193652332400216X/pdfft?md5=266be7abeb36d97ac0e7e0dfe42674e4&pid=1-s2.0-S193652332400216X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142049482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved survival of patients with stage III small-cell lung cancer with primary resection: A SEER-based analysis","authors":"","doi":"10.1016/j.tranon.2024.102070","DOIUrl":"10.1016/j.tranon.2024.102070","url":null,"abstract":"<div><h3>Introduction</h3><p>: Small cell lung cancer (SCLC) is mostly diagnosed in stage III-IV patients and associated with poor prognosis. To date, surgery is no gold-standard treatment for any SCLC stage and evidence is lacking whether it is beneficial. Here we investigate the impact of surgery, with special attention to stage III SCLC patients, sub-stages and treatment combinations.</p></div><div><h3>Methods</h3><p>: The overall survival (OS) and cancer-specific survival (CSS) of 33,198 SCLC patients (SEER database) were analyzed retrospectively, using various statistical analyses, including propensity score matching (PSM), recursive partitioning, and sequential landmark analyses.</p></div><div><h3>Results</h3><p>: Independent of stage, the OS of patients with surgery-including treatments was almost always better than without surgery. This holds true for stage I-II patients, even after PMS analysis (<em>p</em> &lt; 0.017). The same was found for stage IV patients that underwent surgery plus chemotherapy vs. chemotherapy alone (<em>p</em> = 0.013 after PSM). Stage III patients showed a robust improvement in OS and CSS after surgery (OS: 18 vs.13 months) or surgery plus chemotherapy (OS: 20 vs.15 months) as confirmed by well-balanced PSM and sequential landmark analyses of long-term survivors. More detailed analyses using two independent approaches showed prolonged OS in T3–4/N0–1 and T1–2/N2 stage III patients after surgery or surgery plus chemotherapy. Importantly, primary site surgery had a major survival advantage over surgery at regional sites (<em>p</em> &lt; 0.003).</p></div><div><h3>Conclusion</h3><p>: Our study demonstrates that selected patients of all stages, including stage III T3–4/N0–1 and T1–2/N2, can benefit greatly from surgery-including treatments. Thus, surgery should be included into hospital treatment recommendations for specifically selected SCLC patients.</p><p>Condensed abstract</p><p>Primary resection in patients with stage III SCLC needs re-evaluation. Selected patients with stage III SCLC benefit significantly from surgery. Patients with T3–4/N0–1 and T1–2/N2 stage III SCLC should be considered for surgery.</p></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1936523324001979/pdfft?md5=3f60384004127af0c305b97a92c7fc01&pid=1-s2.0-S1936523324001979-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low cytoplasmic NUB1 protein exerts hypoxic cell death with poorer prognosis in oestrogen receptor negative breast cancer patients","authors":"","doi":"10.1016/j.tranon.2024.102106","DOIUrl":"10.1016/j.tranon.2024.102106","url":null,"abstract":"<div><p>Current prognostic biomarkers fall short in stratifying Oestrogen receptor (ER)-negative breast cancer patients regarding tumour progression risk at diagnosis. The role of AIPL1 in activating its tumour suppressor client protein, NEDD8 Ultimate Buster-1 (NUB1) remains unknown in cancer. Our study demonstrated how downregulated AIPL1 results in the deactivated NUB1 protein under hypoxic conditions. We examined the AIPL1-NUB1 pathway<em>in vitro</em> using cell lines i.e. MCF-7, MDA-MB-231, RCC4 <em>etc.</em> NUB1 expression was assessed using Oncomine, and cBioPortal was performed to assess NUB1′s prognostic significance in human cancers. In the John Radcliffe Hospital cohort (<em>n</em> = 122), immunohistochemistry analysis revealed downregulated AIPL1 (Log2 fold change=-0.28; <em>p</em> &lt; 0.001) and upregulated NUB1 transcripts (Log2 fold change=0.59; <em>p</em> &lt; 0.001) compared to adjacent normal tissues. In severe chronic hypoxia, multimerised AIPL1 localisedin the cytoplasm while NUB1 protein migrated to the nucleus, where the absence of NUB1 nuclear localisation led to cell cycle arrest. Biopsies showed that patients with lower cytoplasmic NUB1 expression (<em>n</em> = 57) had poorer overall survival compared to those with higher cytoplasmic expression (<em>n</em> = 57), HR=1.78; 95 % CI=1.01–3.35, <em>p</em> = 0.048. Low NUB1 protein levels in both normoxic and hypoxic conditions were associated with cell cycle arrest and upregulation ofp21 and p27 in breast cancer cell lines, correlating significantly withpoorer survival outcomes in all breast cancer and ER-negative breast cancer patients.</p></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S193652332400233X/pdfft?md5=34aa4596a11e4f53664b82cf0e7e9dcb&pid=1-s2.0-S193652332400233X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircCOCH plays a critical role in Hepatocellular carcinoma through modulating miR-450a and activating PI3K/mTOR pathway","authors":"","doi":"10.1016/j.tranon.2024.102090","DOIUrl":"10.1016/j.tranon.2024.102090","url":null,"abstract":"<div><p>Hepatocellular carcinoma (HCC) is a primary liver cancer with high pathogenicity and extremely poor prognosis. The role of circular RNAs (circRNAs) in HCC carcinogenesis and progression remains to be determined. Based on the analysis of HCC-related databases, as well as the expression analysis and identification of 25 HCC patient tissues and HCC cell lines, we found that the hsa_circ_0031431 (circCOCH) is significantly highly expressed in HCC tissues and cell lines. High circCOCH expression is associated with enhanced tumor proliferation and metastasis, and knocking down circCOCH can inhibit the growth of HCC in vivo and in vitro. Mechanistic studies show that circCOCH upregulates the expression of epidermal growth factor receptor (EGFR) through sponge miR-450a, thereby activating the Phosphoinositide 3-kinases (PI3Ks) cell pathway to promote HCC proliferation and metastasis. Futhermore, we found that <em>IGF2BP3</em> mediates the biogenesis of circCOCH. The present study provides innovative insights into the role of circRNAs in the etiology of HCC carcinogenesis and might serve as a new promising therapeutic target for HCC.</p></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1936523324002171/pdfft?md5=4fc68759808e87f59273a99d7f9e53f4&pid=1-s2.0-S1936523324002171-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142049439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the chemotherapeutic potential of taxifolin ruthenium-p-cymene complex in breast carcinoma: Insights into AhR signaling pathway in vitro and in vivo","authors":"","doi":"10.1016/j.tranon.2024.102107","DOIUrl":"10.1016/j.tranon.2024.102107","url":null,"abstract":"<div><h3>Background</h3><p>Mammary carcinoma is the most frequently diagnosed form of carcinoma in women worldwide. The organometallic compounds showed a prospective anticancer activity. This research explored the anticancer efficacy of taxifolin ruthenium-p-cymene counter to breast cancer.</p></div><div><h3>Methods</h3><p>The anticancer efficacy of the novel organometallic compound was investigated via various in vitro and in vivo techniques using breast cancer cell lines and breast cancer model of rat.</p></div><div><h3>Results</h3><p>Target proteins were identified via pharmacophore analysis, which revealed a high binding affinity towards AhR, EGFR, and β-catenin. The compound induced apoptotic events and prevented cancer cell colony formation. Furthermore, decreased expression of AhR, EGFR, and N-cadherin inhibited cancer cell growth, migration, and proliferation. The compound provoked the cell cycle arrest at sub G0/G1 phase, S phase and G2/M phase and inaugurated the caspase-3 dependent apoptotic events. The in-vivo experimentation displayed the fruitful restoration of breast tissue since the complex treatment in DMBA persuaded breast carcinoma in rat. Moreover, the upstream of p53 and caspase-3 expression along with substantially downstream of vimentin, β-catenin, m-TOR and Akt expression.</p></div><div><h3>Conclusions</h3><p>In conclusion, the compound repressed the cancerous cellular viability, migration, and EMT via modulating the AhR/EGFR/ PI3K transduction pathway and the expression of EMT biomarkers such as N-cadherin, E-cadherin, thus eventually revoked the EMT facilitated metastasis of malignant cells.</p></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1936523324002341/pdfft?md5=a6b9eb5637256c48a02fb5f57e121b50&pid=1-s2.0-S1936523324002341-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142044593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}