tbuckley/cabot-search huggingface dataset:
Abstract 6684: Aiolos expression regulates epithelial-mesenchymal transition through repressing miR-424-5p in lung cancer cells
Authors: Ying-Shiun Kao, Jung-Jyh Hung
Journal: Cancer Research (2025)

Abstract Introduction: Epithelial-mesenchymal transition (EMT) is one of the major molecular mechanisms inducing tumor invasion and metastasis. The Ikaros family of DNA binding proteins are zinc finger transcription factors. Aiolos overexpression promotes EMT through upregulating the PI 3-kinase/Akt/Twist/MMP16 pathway in lung cancer. However, the roles of Aiolos regulating EMT and metastasis through miRNAs expression in lung cancer has not been well demonstrated in the literature. Materials and Methods: qRT-PCR was performed to determine miR-424-5p expression in H1299-Aiolos and A549-Aiolos cells. Knockdown of miR-424-5p was performed in H1299 cells, and transfection of miR-424-5p was performed in A549 cells. Western blotting analysis was performed to demonstrated E-cadherin and vimentin expression. Migration assay and matrigel invasion assay were done to determine the EMT phenotypes after miR-424-5p transfection or knockdown in lung cancer cells. Results: Down-regulation of miR-424-5p in H1299-Aiolos and A549-Aiolos cells was determined by qRT-PCR. Western blotting analysis showed decreased E-cadherin and increased vimentin expression in H1299 cells after miR-424-5p knockdown. Western blotting analysis also showed increased E-cadherin and decreased vimentin expression in A549 cells after miR-424-5p transfection. Migration assay showed that migration increased in H1299-shmiR-424-5p cells, but decreased in A549-miR-424-5p cells. Matrigel invasion assay showed the invasiveness increased in H1299-shmiR-424-5p cells, but decreased in A549-miR-424-5p cells. Conclusions: Aiolos expression regulates EMT through repressing miR-424-5p expression in lung cancer cells. The results shed light on further understanding of the mechanisms of metastasis in lung cancer. Citation Format: Ying-Shiun Kao, Jung-Jyh Hung. Aiolos expression regulates epithelial-mesenchymal transition through repressing miR-424-5p in lung cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6684.
Abstract 5377: FGF1 regulates breast cancer growth and metabolic reprogramming through ETV4
Authors: Barbara Mensah Sankofi, Stevi Johnson Murguia, William L. Berry, Elizabeth A. Wellberg
Journal: Cancer Research (2025)

Abstract Breast cancer is the most frequently diagnosed cancer in women worldwide. Obesity increases resistance to breast cancer therapies and patient mortality, particularly for estrogen receptor-positive (ER+) tumors that represent 70% of all cases. Adult weight gain in women with obesity, characterized by adipose tissue expansion, is an independent prognostic factor for breast cancer. In a preclinical model, we found that weight gain promoted ER+ tumor growth after endocrine therapy through adipose-derived fibroblast growth factor 1 (FGF1). To determine the underlying mechanisms, we used cultured ER+ breast cancer cells (MCF7, tamoxifen-resistant MCF7 cells, and UCD12 cells) treated with FGF1, combined with gene expression profiling and metabolic analysis. ETS variant 4 (ETV4), which regulates ER activity and cancer cell glycolysis, was the top gene induced by FGF1 in multiple ER+ lines. ETV4 was shown by others to regulate breast cancer metabolism and stemness, contributing to disease progression. We hypothesized that ETV4 mediates the FGF1-dependent effects on breast cancer glycolytic reprogramming in obesity-associated breast tumors. ETV4 was upregulated in human PDX tumors grown in obese versus lean mice. In invasive human breast cancer specimens, high versus low ETV4 expression predicted a shorter recurrence-free survival for patients with ER+ tumors. ETV4 knockdown in cultured endocrine-resistant breast cancer cells prevented the proliferation and induction of glycolytic genes with FGF1 treatment. Conversely, overexpression of ETV4 was sufficient to increase glycolytic gene expression and enzyme activity, as well as cell proliferation. Taken together, our data suggest a mechanism by which FGF1 supports breast cancer endocrine therapy resistance in the context of obesity through ETV4 induction and glycolytic metabolic reprogramming. Understanding this process may aid in designing effective treatments, especially for patients resistant to current ER-targeted therapies. Furthermore, ETV4 may be a biomarker to identify breast tumors with excess FGF signaling and patients at high risk for progression. Citation Format: Barbara Mensah Sankofi, Stevi Johnson Murguia, William L. Berry, Elizabeth A. Wellberg. FGF1 regulates breast cancer growth and metabolic reprogramming through ETV4 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5377.
Abstract 7131: Integrative single-cell transcriptomic and epigenomic immune profiling reveals parallel insights into cancer research
Authors: Errile Pusod, Patricia Schnepp, Srikanth Perike, Angelica Olcott, Elizabeth Dreskin
Journal: Cancer Research (2025)

Abstract Introduction: Single-cell technologies have revolutionized immune profiling by enabling the detailed analysis of individual cells, uncovering cellular heterogeneity and complex regulatory mechanisms. Two common single-cell omics include single-cell RNA-sequencing (scRNA-seq) which profiles gene expression by capturing mRNA transcripts, and single-cell ATAC sequencing (scATAC-seq) which profiles gene regulation using hyperactive Tn5 transposase to assess chromatin accessibility. In this workflow, we demonstrate integrative analysis of both technologies that provides comprehensive view of a cell’s transcriptomic and epigenomic landscapes. Methods: Two independent scRNA-seq and scATAC-seq workflows were performed on peripheral blood mononuclear cells (PBMCs) and various cancer cell lines to provide accessible and convenient model system for various oncology applications. Libraries were prepared using Bio-Rad ddSEQ 3’ scRNA-seq and scATAC-seq Kits, which uses droplet-based ddSEQ technology for capturing cells with high sensitivity and recovery. Libraries were sequenced using Illumina NextSeq 2000. Data quality was assessed using the Omnition Analysis Software and Seurat was used for downstream tertiary analyses. Results: Here, we present an integrated analysis of scRNA-seq and scATAC-seq for comprehensive immune profiling of peripheral blood mononuclear cells (PBMCs) and various cancer cell lines. Our findings show consistent correlation of cell types and subtypes identified from each pair of samples. Furthermore, specific differentially expressed genes (DEGs) and differentially accessible regions (DARs) were found to be shared in corresponding cell types such as chromatin peak and increased gene expression of Epiregulin (EREG) in CD14+ monocytes. Conclusion: Bio-Rad ddSEQ 3’ scRNA-seq and scATAC-seq kits provide affordable and scalable method for profiling immune response from thousands of individual cells with increased sensitivity and accuracy. Combined analyses from these two approaches show strong potential for oncology applications. For example, the ability to identify novel immune cell subsets, discover tumor biomarkers, characterize tumor-infiltrating lymphocytes, and reveal regulatory elements driving immune responses in the tumor microenvironment can all be achieved. Citation Format: Errile Pusod, Patricia Schnepp, Srikanth Perike, Angelica Olcott, Elizabeth Dreskin. Integrative single-cell transcriptomic and epigenomic immune profiling reveals parallel insights into cancer research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7131.
Abstract 6685: miR-148a-3p acts as a potential radiosensitizer through integrin signaling pathway in head and neck cancer
Authors: Thien-Hoang Pham, Ming-Hua Wang, Tai-Yu Kuo, An-Lun Li, Kun-Lin Wu, Ching-Yun Chen, Nianhan Ma
Journal: Cancer Research (2025)

Abstract Radioresistance remains an unsolved challenge in cancer treatments and links to radiation-induced bystander effects (RIBEs), hence facilitating tumorigenesis or metastasis. In our previous study, miR-148a-3p expression in plasma from head and neck cancer patients was related to radiotherapy. This study explored the roles of miR-148a-3p in radiation response and RIBEs while introducing a radiosensitizer in head and neck cancer. Radiation for cultured cells was provided by the Radiation Oncology Department at Landseed International Hospital. The in vitro study demonstrated how miR-148a-3p regulates cancer cell functions and DNA damage responses. Exosomes were isolated from conditioned media (CM) using chromatographic columns. To generate the radiosensitizer, exosomes from Wharton's Jelly Mesenchymal Stem Cells (WJMSCs) were combined with miR-148a-3p mimics and sonicated. Following radiation, miR-148a-3p expression was decreased. The gain-of-function studies revealed that miR-148a-3p enhanced radiosensitivity by reducing cell proliferation and migration after radiation, promoting DNA damage and genomic instability, and inducing the G2/M phase arrest. Conversely, the miR-148a-3p sponges diminished the radiosensitivity of cancer cells. Furthermore, we perceived that miR-148a-3p was implicated in the RIBEs. Specifically, high miR-148a-3p levels in CM from irradiated cells effectively inhibited the RIBE-induced proliferation and migration of non-irradiated cancer cells. Consequently, we observed increased levels of miR-148a-3p in exosomes secreted by irradiated cells if we overexpressed miR-148a-3p mimics and exosomal miR-148a-3p suppressed cell migration and invasion, and also promoted DNA damage and genomic instability in non-irradiated cancer cells. In addition, the luciferase assay revealed that ITGA5, a member of integrin receptor family involved in various malignancies, is a direct target of miR-148a-3p. The upregulation of ITGA5 counteracted the radiosensitivity of miR-148a-3p, while ITGA5 knockdown increased radiation sensitivity. Finally, miR-148a-3p was loaded into WJMSC-derived exosomes to develop a radiosensitizer agent, which eliminated cancer cell migration during radiotherapy. This research indicated that miR-148a-3p enhanced the radiosensitivity and prevented RIBE activities in head and neck cancer cells by regulating ITGA5, suggesting a promising therapeutic radiosensitizer for head and neck cancer. Citation Format: Thien-Hoang Pham, Ming-Hua Wang, Tai-Yu Kuo, An-Lun Li, Kun-Lin Wu, Ching-Yun Chen, Nianhan Ma. miR-148a-3p acts as a potential radiosensitizer through integrin signaling pathway in head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6685.
Abstract 6967: Suppression of protein X-mediated survivin expression enhance the antitumor effect of irinotecan in colorectal cancer
Authors: Se Yong Park, Ju-Hee Kang, Jung Ho Hwang, Sun-Ju Lee, Jun-Won Yun, Seung Hyun Oh
Journal: Cancer Research (2025)

Abstract Survivin, an inhibitor of apoptosis protein, contributes to cancer drug resistance. This study investigated survivin's role in irinotecan resistance in colorectal cancer. RT-PCR and western blotting confirmed increased survivin expression in irinotecan-treated colorectal cancer cells. Knockdown of survivin by using siRNA decreased cell viability, confirming its anti-apoptotic function. Screening potential upstream regulators revealed ‘protein X’ but not ‘protein Y’, as a key mediator of survivin expression. ‘Protein X’ is overexpressed in many cancers and associated with drug resistance. We hypothesized that inhibiting ‘protein X’ could enhance irinotecan's effectiveness. Both genetic inhibition by siRNA and pharmacological inhibition with an ‘protein X’ inhibitor enhanced apoptotic effects of irinotecan in colorectal cancer cell lines. The synergistic effect was particularly pronounced in HCT116 cells, which showed the highest sensitivity to irinotecan. These findings suggest that targeting ‘protein X’-mediated survivin expression may be a promising strategy to overcome irinotecan resistance in colorectal cancer. This approach provides a novel perspective on enhancing the efficacy of irinotecan-based therapies and potentially improving outcomes for colorectal cancer patients. Further in vivo studies and clinical trials are warranted to validate these findings and explore the therapeutic potential of this combination approach. Citation Format: Se Yong Park, Ju-Hee Kang, Jung Ho Hwang, Sun-Ju Lee, Jun-Won Yun, Seung Hyun Oh. Suppression of protein X-mediated survivin expression enhance the antitumor effect of irinotecan in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6967.
Abstract 5139: PP2A-B56a as a critical regulator of cellular plasticity and epithelial-to-mesenchymal transition
Authors: Brittany N. Heil, Claire M. Pfeffer, Garima Baral, Mei B. Bahler, Anna K. Darling, Sydney J. Clifford, Brittany L. Allen-Petersen
Journal: Cancer Research (2025)

Abstract Metastasis is the major cause of death in cancer patients including lung cancer, the leading cause of cancer-related deaths in the United States. Fifty percent of patients have metastatic disease at the time of diagnosis, plummeting the 5-year survival rate from 26% to just 9%, demonstrating a critical gap in our understanding of the contributing cell signaling pathways. Epithelial-to-Mesenchymal Transition (EMT) is an important initiating step in metastasis, allowing cells to become more migratory and invasive to establish secondary tumors in distant locations. Previous studies have identified transcriptional reprogramming as the main driver of EMT. While transcription factors are important in this cell state switch, there are many factors that contribute to EMT outside of transcriptional regulation, such as post-translational modifications (PTMs). PTMs, such as phosphorylation, play a large role in cell signaling that can impact cellular identity and plasticity, yet these modifications are largely understudied, particularly in the context of EMT. The serine/threonine phosphatase, Protein Phosphatase 2A (PP2A), is a vital phosphatase, accounting for 50% of serine/threonine phosphatase activity in the cell. PP2A is a heterotrimeric complex consisting of a scaffolding subunit (A), a catalytic subunit (C), and regulatory subunit (B) which determines substrate specificity. Though PP2A has previously been shown to play a role in cell state regulation and EMT, the contribution of the individual B subunits is unknown. PP2A-B56α has previously been implicated in tumor suppression and the regulation of cellular plasticity. Through the use of 2D immunofluorescence, western blot analysis, and 3D invasion assays, our in vitro studies show that loss of PP2A-B56α leads to a significant alteration in cell identity, demonstrated by a reduction in epithelial markers (E-cadherin) and an increase in mesenchymal markers (Vimentin). These shifts in cell markers also correlate with enhanced migratory and invasive capabilities in vitro and are recapitulated in vivo via tail vein invasion assay. Collectively, these findings highlight PP2A-B56α as a key regulator of cellular plasticity and EMT in lung cancer. Citation Format: Brittany N. Heil, Claire M. Pfeffer, Garima Baral, Mei B. Bahler, Anna K. Darling, Sydney J. Clifford, Brittany L. Allen-Petersen. PP2A-B56a as a critical regulator of cellular plasticity and epithelial-to-mesenchymal transition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5139.
Abstract 7138: Whole genome sequencing-based detection of minimal residual disease using individual-specific features
Authors: Jun Hyeok Lim, Jeong-Seon Ryu, Ji Won Byun, Jongsuk Chung, Hyun-Tae Shin
Journal: Cancer Research (2025)

Abstract The detection of minimal residual disease (MRD) following cancer treatment is critical for preventing recurrence and improving patient prognosis. However, existing MRD detection methods often lack the sensitivity required for precise monitoring. We have developed a highly sensitive method for MRD detection using whole-genome sequencing (WGS) analysis of cell-free DNA (cfDNA) with individual-specific features. The approach begins by identifying consensus single nucleotide variants (SNVs) and fusions that are consistently detected by multiple variant callers in the patient’s tumor WGS. Using a novel algorithm, we quantify supporting reads at the consensus SNV positions and assess their statistical significance based on the error distribution in the patient’s plasma WGS. Additionally, unique sequences corresponding to the consensus fusion positions in the plasma WGS are detected to diagnose MRD. Validation through cancer cell-line mix experiments demonstrated a sensitivity of less than 1:12, 800. Furthermore, the method effectively detected MRD in clinical samples from various cancer types, including lung, melanoma, breast, and liver. The limit of detection for the SNV quantification method was determined by the error rate in the individual BAM file, while the fusion sequence detection method exhibited no detection limit due to a limit of blank of zero. This algorithm has been implemented on a cloud platform, allowing individual users to analyze their data by uploading it. This highly sensitive approach for detecting MRD offers the potential to improve cancer patient prognosis significantly. Moreover, this technology holds great promise for broad applicability across various cancer types where cfDNA-based monitoring can provide clinical benefits. Citation Format: Jun Hyeok Lim, Jeong-Seon Ryu, Ji Won Byun, Jongsuk Chung, Hyun-Tae Shin. Whole genome sequencing-based detection of minimal residual disease using individual-specific features [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7138.
Abstract 6980: Discovery of a subtype-selective TEAD inhibitor for cancer treatment
Authors: Won An, YoungKu Kang, Seul Lee, Ye Gi Han, Jiyoon Seok, Sanghoon Kim, Ahreum Kwon, Eunji Ha, Bora Yoo, Ji-Duck Kim, Joon Seok Park
Journal: Cancer Research (2025)

Abstract The transcriptional enhanced associated domain (TEAD) in the Hippo pathway signaling can regulate development and tumorigenesis. TEAD transcription factors have four subtypes (TEAD1-4) with highly conserved sequence whereas these subtypes show different expression levels depending on the organ. TEAD inhibitors are the emerging therapeutic agents for patients with NF2 mutant tumors. Most TEAD inhibitors block all subtypes of TEAD by targeting palmitoylation site and the interface 3 of YAP and TEAD. Here, we discovered TEAD selective inhibitors targeting the allosteric position of palmitoylation site. Our bicyclic compounds showed the potent in vitro activities on TEAD and cancer cell growth inhibitory effects. We also identified the compound-protein structure through X-ray crystallography and the effect of imidazole part on the TEAD selectivity. Pharmacokinetic properties of TEAD selective inhibitors were acceptable for oral administration. Furthermore, a TEAD selective inhibitor reduced the tumor growth of NCI-H226 xenograft mouse model. Overall, a TEAD selective inhibitor has the potential for developing targeted therapy for NF2 mutant tumors also each TEAD subtype-driven pathologies. Citation Format: Won An, YoungKu Kang, Seul Lee, Ye Gi Han, Jiyoon Seok, Sanghoon Kim, Ahreum Kwon, Eunji Ha, Bora Yoo, Ji-Duck Kim, Joon Seok Park. Discovery of a subtype-selective TEAD inhibitor for cancer treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6980.
Abstract 6979: Development of orally bioavailable multi-targeted inhibitors of Wnt signaling for the treatment of colorectal cancer
Authors: Sean Ginn, Samantha Rokey, Alessandra Fistrovich, Aidan McMahon, Timothy Chavez, Vasudha Tandon, Joaquina Nogales, Carly Cabel, Crystal Morales, Shravani Daptardar, Curtis Thorne, Sourav Banerjee, Christopher Hulme
Journal: Cancer Research (2025)

Abstract Colorectal cancer (CRC) is a leading cause of cancer-related deaths in the United States, projected to account for 7.6% of all new U.S. cancer cases in 2024. Hyperactivation of the Wnt/β-catenin signaling pathway is a key driver of CRC, with up to 96% of cases showing oncogenic Wnt activation. Increased Wnt activation contributes to tumor stemness, progression, and pathogenesis. Targeted therapies have been developed, but drug resistance can often occur, limiting effectiveness. In this work, a novel series of multi-targeted kinase inhibitors that target downstream members of the Wnt signaling pathway (DYRKs, CLKs, CDK7/8/19), along with PI3Kα, BRAF, and PDGFR have been developed. Our lead compound, DYR895, demonstrates improved Wnt signaling inhibition over phase 1b clinical candidate Cirtuvivint (WNT reporter EC50: 5.1 nM vs. 230 nM), while being well tolerated in mouse models (MTD &amp;gt;50 mg/kg) and orally bioavailable (F%: 81%). In an HCT-116 xenograft model, treatment with DYR895 resulted in reduced tumor growth and improved survival. Further optimization of DYR895 with the goal of reducing CNS exposure while enhancing Wnt inhibition led to the discovery of DYR1055, with a 10x improvement in affinity for some target kinases while maintaining key surrogate ADME attributes. Investigations into the efficacy of DYR1055 in disease models are ongoing. Citation Format: Sean Ginn, Samantha Rokey, Alessandra Fistrovich, Aidan McMahon, Timothy Chavez, Vasudha Tandon, Joaquina Nogales, Carly Cabel, Crystal Morales, Shravani Daptardar, Curtis Thorne, Sourav Banerjee, Christopher Hulme. Development of orally bioavailable multi-targeted inhibitors of Wnt signaling for the treatment of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6979.