bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 278: Investigating the functional role of cancer-associated fibroblasts in the emergence of drug-tolerant persisters in ovarian cancer
Authors: Ng Angel S. , Bui Ngoc , Ailles Laurie 
Published: March 2024

Abstract
Chemoresistance remains a major clinical challenge for the treatment of high-grade serous ovarian cancer (HGSC), the most lethal gynecologic malignancy. The majority of patients who initially respond to first-line platinum/taxane-based chemotherapy eventually relapse with chemoresistant disease, leading to poor survival outcomes. It is increasingly recognized that cancer cells can enter a reversible drug-tolerant persister (DTP) state through non-genetic mechanisms to evade chemotherapy-induced cytotoxicity prior to the development of chemoresistance. However, how environmental signals and extracellular factors from the tumor microenvironment drive the process remains poorly understood. Cancer-associated fibroblasts (CAFs) are a functionally heterogeneous population of activated fibroblasts. CAFs play a critical role in shaping the tumor microenvironment and tumor behaviors, including promoting tumor growth and mediating therapy resistance. Here, we demonstrated that HGSC cell lines co-cultured with patient-derived FAP-high CAFs, a subpopulation of CAFs previously identified in our lab to be tumor-promoting, significantly increase the formation of DTPs upon prolonged carboplatin treatment compared to the mono-cultured condition. Interestingly, the extracellular matrix (ECM) organization signature is enriched in FAP-high CAFs compared to their FAP-low counterparts, and we found that ECM deposited by FAP-high CAFs also facilitates the emergence of DTPs in HGSC cells. Future work will focus on elucidating the mechanisms by which FAP-high CAFs and the associated ECM promote DTP formation in HGSC cells through transcriptomic and proteomic profiling. This will aid the identification of potential therapeutic vulnerabilities to target cancer cells in the DTP state in FAP-high HGSC patients.
Citation Format: Angel S. Ng, Ngoc Bui, Laurie Ailles. Investigating the functional role of cancer-associated fibroblasts in the emergence of drug-tolerant persisters in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 278.
Abstract 2789: NCAPG promotes triple-negative breast cancer stemness by a positive feedback loop with HIF-1α
Authors: Zhang Huimin , Xie Peiling , An Rui 
Published: March 2024

Abstract
Objective: Triple-negative breast cancer (TNBC) is life-threatening because of limited therapies and lack of effective therapeutic targets. NCAPG, an oncogenic marker, might be served as a new target for TNBC treatment. Here, we aimed to elucidate the role of NCAPG played in TNBC and the underlying mechanism.
Design: GEO data was used to investigate the potential targets for TNBC. Patient samples and TCGA data were used to demonstrate the clinical significance. Cell migration, self-renewal ability, chemoresistance and expression of pluripotency factors were tested to detect the stemness of TNBC cells. Immunoprecipitation, ubiquitination assay and chromatin immunoprecipitation assay were utilized to investigate the mutual regulation mechanism of NCAPG and HIF-1α.
Results: NCAPG was significantly overexpressed in TNBC compared with other subtypes of breast cancer and was positively correlated with poor overall survival. Elevated NCAPG expression could enhance cancer stem-like cell properties of TNBC cells. Mechanically, NCAPG positively regulated HIF-1α protein stability by interacting with HIF-1α and competitively abrogating the E3 ligase FBXW7-mediated ubiquitination and degradation towards HIF-1α. NCAPG, as a direct target gene of HIF-1α, could be in turn transcriptionally upregulated by HIF-1α.
Conclusion: NCAPG promotes TNBC stemness by a HIF-1α/NCAPG positive feedback loop. NCAPG is a promising target for TNBC treatment.
Citation Format: Huimin Zhang, Peiling Xie, Rui An. NCAPG promotes triple-negative breast cancer stemness by a positive feedback loop with HIF-1α [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2789.
Abstract 2791: Establishment of immortalized endometrial cell lines using Sendai virus
Authors: Hikino Kohei , Komatsu Hiroaki , Hichiwa Genki , Kazuki Kanako , Kazuki Yasuhiro , Kugoh Hiroyuki , Okawa Masayo , Ida Yuki , Hosokawa Masayo , Sawada Mayumi , Kudoh Akiko , Sato Shinya , Taniguchi Fuminori 
Published: March 2024

Abstract
Objective: To establish endometrial immortalized cell lines using the Sendai virus and analyze their characteristics.
Methods: The study included patients with benign ovarian tumors and endometrioid carcinoma who had regular menstrual cycles. Endometrial cells were collected and separated into epithelial and non-epithelial cells using flowcytometry (FCM) (CD326 (EpCAM) antibody). Furthermore, the isolated cells were infected with Sendai virus carrying three immortalization genes (Bmi-1, hTERT, and SV40T) to create immortalized cell lines. The cells were characterized as epithelial cells by immunocytochemistry (ICC), and receptor expression was assessed by reverse transcription PCR (RT-PCR) and ICC. Non-epithelial cells from the patients with endometrial carcinoma were evaluated using ICC.
Results: The immortalized cell lines were capable of more than 20 passages. Immortalized endometrial epithelial cells tested positive for anti-Keratin antibodies and negative for anti-Vimentin antibodies by ICC. Additionally, FCM detected these cells as positive for anti-EpCAM antibody, confirming that they were epithelial cells. RT-PCR confirmed mRNA expression of estrogen α-receptor and progesterone receptor after 20 passages and ICC confirmed protein expression of them after 10 passages, establishing an endometrial epithelial immortalized cell line. Non-epithelial cells isolated from patients with endometrial carcinoma tested positive for anti-α-smooth muscle actin and anti-Vimentin antibodies by ICC, indicating their characterization as cancer-associated fibroblasts.
Conclusion: We successfully established an immortalized cell line of endometrial epithelial cells using Sendai virus and generated cancer-associated fibroblasts.
Citation Format: Kohei Hikino, Hiroaki Komatsu, Genki Hichiwa, Kanako Kazuki, Yasuhiro Kazuki, Hiroyuki Kugoh, Masayo Okawa, Yuki Ida, Masayo Hosokawa, Mayumi Sawada, Akiko Kudoh, Shinya Sato, Fuminori Taniguchi. Establishment of immortalized endometrial cell lines using Sendai virus [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2791.
Abstract 2807: Distinctive microbiome signatures in colorectal cancer: A comparative metagenomic analysis
Authors: Chen Ziqi , Nie Bei Ning , Luo Bin , Wang Ziliang , Wang Xinyi 
Published: March 2024

Abstract
The human gut microbiome is increasingly recognized for its role in colorectal cancer (CRC) pathogenesis. This study aims to delineate the microbiome characteristics of CRC patients compared to healthy individuals, using a comprehensive metagenomic approach.
We utilized a cohort of 80 CRC patients and an equal number of matched healthy controls. Fecal samples were collected and subjected to in-depth metagenomic sequencing, targeting both structural and functional profiles of the microbiome. Data analysis involved advanced bioinformatics techniques. Key observations were subsequently validated in an independent cohort to bolster the findings.
Our analysis revealed significant alterations in the microbiome composition of CRC patients versus healthy individuals. Notably, there was an increased prevalence of pathogenic bacteria, such as Bacteroides Vulgatus in CRC patients. These bacteria are implicated in promoting inflammation and carcinogenesis. Conversely, there was a noticeable depletion of beneficial microbes like Lactobacillus in the CRC group. Functionally, the microbiome in CRC patients was characterized by enriched pathways related to DNA repair, cell cycle control, and metabolism pathways like Citrate cycle and Galactose metabolism. Validation in an independent cohort confirmed these distinctive microbiomic patterns.
Our study provides compelling evidence of altered microbiome landscapes in CRC patients, highlighting potential roles in disease development and progression. These findings pave the way for further investigation into microbiome-based diagnostics and therapeutic interventions in colorectal cancer.
Citation Format: Ziqi Chen, Bei Ning Nie, Bin Luo, Ziliang Wang, Xinyi Wang. Distinctive microbiome signatures in colorectal cancer: A comparative metagenomic analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2807.
Abstract 290: The role of tumor stromal topography-regulated genes in modulating the cellular landscape of tumor stroma in breast cancer
Authors: Su Chia-Yi 
Published: March 2024

Abstract
The tumor remodels the surrounding extracellular matrix fibers to become topographically aligned at the tumor front, further facilitating cancer cell migration. Our recent studies show that aligned tumor stromal topography promotes the detachment of breast cancer cells from the main tumor, then, in the following cell migration, upregulating genes such as genes encoding the cytochrome P450 family 1 subfamily A member 1 (CYP1) and inhibitor of DNA binding (ID) proteins. In this study, we further explored the role of topography-regulated genes in modulating the cellular landscape of tumor stroma. By analyzing the correlation of topography-regulated genes with stromal cell infiltration in bioinformatics databases, we found significant positive correlations between the RNA expression levels of most topography-regulated genes and the infiltration levels of cancer-associated fibroblasts and endothelial cells. Notably, the strongest correlation was between the expression level of ID3 and the infiltration levels of cancer-associated fibroblasts (r = 0.509) and endothelial cells (r = 0.506). Additionally, ID3 remained highly expressed in circulating tumor cells but exhibited low expression at distant metastatic sites. These findings suggest that genes regulated by tumor stromal topography, especially ID3, may play a role in neovascularization and fibrosis of the tumor microenvironment and the survival adaptation of cancer cells in circulation, thereby promoting metastasis.
Citation Format: Chia-Yi Su. The role of tumor stromal topography-regulated genes in modulating the cellular landscape of tumor stroma in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 290.
Abstract 2956: Chemotherapy-induced adipocyte senescence triggers bone loss through osteoclast activation
Authors: Raut Ganesh Kumar , Malachowski Taylor , Holt Taylor , Oliveira Renata , Luo Xianmin , Faget Douglas , Ren Qihao , Stewart Sheila 
Published: March 2024

Abstract
Despite breakthroughs in cancer treatment, chemotherapy-induced osteo-toxicity is a major problem that compromises the quality of life and overall survival of cancer patients regardless of cancer type. Recently we demonstrated that chemotherapy-induced senescence drives bone loss by both limiting mineralization of new bone and increasing bone resorption. However, the underlying mechanism of action remains elusive. Therefore, it is critical that we understand the mechanisms that drive these toxicities and develop approaches to mitigate their severity. To establish whether senescent bone resident cells or systemic responses to chemotherapy drove therapy-induced bone loss, we used a vertebral body transplant (vossicle) model. Using this approach, we found that the specific elimination of senescent cells in L4 and L5 donor vossicles (INK-ATTAC) implanted into wildtype mice, protects from chemotherapy-induced bone loss within the vossicles but not the femur of the recipient mice. This demonstrated that chemotherapy-induced senescence in resident bone cells is responsible for bone loss. To determine which bone resident cell(s) underwent senescence in response to chemotherapy and how their gene expression was impacted, we used the p16-CreERT2-tdTomato mouse model and found that chemotherapy triggers senescence in bone marrow adipocytes. Subsequently, we observed that postnatal fat ablation in adipoqCre-inducible DTR transgenic mice (iDTRADQ) prevented chemotherapy-induced bone loss, indicating senescent adipocytes trigger bone loss. Furthermore, we observed chemotherapy-induced bone loss is attributed to RANKL-mediated high osteoclasts activity. Collectively, our data demonstrate that chemotherapy causes senescence in marrow adipocytes which in turn triggers bone loss via RANKL-mediated osteoclasts activation and bone loss can be protected by eliminating senescent cells.
Citation Format: Ganesh Kumar Raut, Taylor Malachowski, Taylor Holt, Renata Oliveira, Xianmin Luo, Douglas Faget, Qihao Ren, Sheila Stewart. Chemotherapy-induced adipocyte senescence triggers bone loss through osteoclast activation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2956.
Abstract 2980: Exploiting the selenoproteome in uveal melanoma
Authors: Sanders Alyssa , Cunanan Camille , Hartsough Edward 
Published: March 2024

Abstract
Uveal melanoma (UM) is a common intraocular malignancy arising from GNAQ/GNA11 mutations in uveal tract melanocytes. Although primary UM is treatable by radiation and enucleation, half of patients will develop liver metastasis. Unfortunately, patients with metastatic UM have a poor prognosis of approximately one-year - underscoring metastatic UM as one of the deadliest cancers. A strong prognostic indicator for UM liver metastases is a deletion or inactivation of the deubiquitinase BAP1, yet its specific role in disease progression is unclear. Intriguingly, upon BAP1 loss of function, the cysteine importer SLC7A11 is up regulated. Imported cysteine can be converted into glutathione serving as a cofactor for antioxidant enzymes like GPX4, a selenoprotein (SeP). SePs are a protein family characterized by having at least one selenocysteine - a selenium (Se) containing amino acid. Interestingly, the liver serves as a major hub for Se transport via Selenoprotein P (SEPP). The selenocysteine rich SEPP is secreted by hepatocytes and catabolized in recipient cells facilitating synthesis of de novo SeP. Here we hypothesize that mutant BAP1 UM utilizes the liver’s Se rich microenvironment to augment selenoproteome expression to stave off oxidative stress. Using publicly available datasets, we found patients with mutant BAP1 UM have increased expression of antioxidants proteins and genes associated with SeP expression. In a panel of BAP1 expressing and deficient UM cells, we found that BAP1 deficient cells have increased expression of SePs, suggesting a predisposition to resist oxidative stress. In the presence of exogenous Se, UM cell lines upregulate SeP expression indicating the importance of selenium availability for SeP expression. In addition, a hepatocyte cell line, and an ex vivo liver slice co-culture model was used to confirm that SEPP was produced in the liver slices and was associated with increased SeP expression in UM cells. Furthermore, we found that BAP1 null UM cells were more susceptible to GPX4 inhibition compared to wild type cells, suggesting a reliance on SeP expression. Taken together, these findings suggest that the liver associated selenoproteome expression may underpin an oxidative stress-associated therapeutic vulnerability in UM liver metastases.
Citation Format: Alyssa Sanders, Camille Cunanan, Edward Hartsough. Exploiting the selenoproteome in uveal melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2980.
Abstract 2988: TUG1 exosomal lncRNA sponges let-7 miRNA family members and advances prostate cancer
Authors: Marima Rahaba Makgotso , Mbeje Mandisa , Kandhavelu Jeyalakshmi , Penny Clement , Dlamini Zodwa 
Published: March 2024

Abstract
Exosomal long-non coding RNAs (lncRNAs) play an important role in cancer progression and have potential prognostic biomarker potential in several cancers including prostate cancer (PCa). Taurine-upregulated gene 1 (TUG1) is an oncogenic lncRNA overexpressed in PCa. This exosomal lncRNA has been reported to promote PCa migration, invasion and Epithelial-Mesenchymal Transition (EMT). However, TUG1 PCa prognostic mechanisms remain to be elucidated. This study aimed to profile differentially expressed lncRNAs in PCa high-grade tumor cells (PC-3) cells compared to low-grade PCa tumor cells (LNCaP). This was achieved by using a 384-well plate of PCa lncRNA gene panel. A human lncRNA database, LncSEA and other bioinformatics tools were used for annotation and enrichment analysis. RT-qPCR was used to confirm the gene array data. Up or down-regulation of ±2 and p &lt;0.05 were considered significant. Forty two (42%) percent and 14% of lncRNAs were shown to be up and downregulated, respectively. Notably, TUG1 was shown to be upregulated in PC-3 cells from PCR array and RT-qPCR results. Bioinformatics analysis revealed that TUG1 is involved in several cancer hallmarks including apoptosis evasion, migration, invasion and EMT. Furthermore, lncRNA/miRNA complexes regulate a series of oncogenic signaling pathways and this study demonstrated that TUG1 sponges the let-7 miRNA family members (a highly conserved tumor suppressor miRNA family) and promotes PCa progression. Precise mechanisms of TUG1/let-7 axis in PCa prognosis need to be largely elucidated as this may hold potential to understanding lncRNA/miRNA-mediated PCa progression and thus be targeted for novel therapeutics.
Citation Format: Rahaba Makgotso Marima, Mandisa Mbeje, Jeyalakshmi Kandhavelu, Clement Penny, Zodwa Dlamini. TUG1 exosomal lncRNA sponges let-7 miRNA family members and advances prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2988.
Abstract 3033: Oncogenic ETS transcription factors avoid repression by EZH2 and FOXO1 in prostate cancer and Ewing sarcoma
Authors: Downing Nicholas F. , Mills Kaitlyn M. , Hollenhorst Peter C. 
Published: March 2024

Abstract
ETS transcription factors play roles throughout development, aiding in hematopoiesis, blood vessel formation and cell fate. The ETS family is composed of 28 members, all of which share an ETS DNA-binding domain. Chromosomal rearrangements that lead to the overexpression of specific ETS promote oncogenic transformation and tumor development. More than half of prostate tumors are driven by aberrant expression of an ETS protein. Our lab has demonstrated that oncogenic ETS form essential interactions with a ubiquitous RNA-binding protein, EWS, to promote prostate tumorigenesis. A similar mechanism exists in Ewing sarcoma (ES). ES tumors are driven by the expression EWS/ETS fusion proteins. This project focuses on the similarities and differences between oncogenic ETS in prostate cancer and EWS/ETS fusions in Ewing sarcoma.
We compared biological functions of the most common oncogenic ETS in prostate cancer, ERG, and the most common fusion in ES, EWS/FLI1. Both ERG and EWS/FLI1 promoted migration and clonogenic survival in normal prostate epithelial cell lines, RWPE1 and PNT2. These data suggest that the EWS-ERG complex and EWS/FLI1 fusion protein can function similarly in prostate cells. Knockdown of endogenous EWS/FLI1 in the ES cell line, A673, reduced anchorage-independent colony formation in soft agar. Rescue with exogenous EWS/FLI1 or EWS/ERG restored colony formation relative to control. Wildtype ERG was unable to rescue colony formation in A673. This suggests that ERG and EWS/FLI1 function differently in A673 cells. Pulldown assays from A673 lysates reveal that ERG interacts with EZH2 and FOXO1. Our lab has established that ERG acts as a transcriptional repressor through the formation of an ERG-EZH2-PRC2 complex. Others demonstrate that FOXO1 represses ERG activity by reducing its recruitment to the target sites. Both the N-terminal truncation of ERG and phosphorylation of ERG at S96 disrupted these interactions and rescued anchorage independent growth in A673 ES cells. These data suggest that EWS/ETS fusions avoid transcriptional repression in Ewing tumors due to loss of the N-terminus of the ETS protein.
Citation Format: Nicholas F. Downing, Kaitlyn M. Mills, Peter C. Hollenhorst. Oncogenic ETS transcription factors avoid repression by EZH2 and FOXO1 in prostate cancer and Ewing sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3033.
Abstract 3039: Pan cancer therapeutic inhibition of oncogenic c-MYC by the engineered destabilized 3’UTR of c-MYC
Authors: Awah Chidiebere U. 
Published: March 2024

Abstract
c-MYC is a master transcription factor that is over expressed in more than 70% of human cancers. There is no clinically approved direct inhibitor of c-MYC. Recently, we reported the development of the engineered destabilized 3’UTR of MYC constructs which is a novel mRNA overwriting technology through which we directly destabilized and degraded c-MYC. Here we report that we have extended this technology in directly targeting and degrading c-MYC in multiple ethnically diverse triple negative breast cancer cell lines, ovarian cancers, neuroendocrine prostate cancers and pancreatic cancers. The constructs are specific, titratable, and directly engaged the c-MYC target validated by RNA transcript technologies. We have performed head-to-head IC50 dose dependent titration comparison with the engineered destabilized 3’UTR of c-MYC constructs and chemotherapies (DNA damaging agents, microtubules inhibiting drugs, alkylating agents) as well as immune checkpoint inhibitor. We found evidence that suggests that the engineered destabilized 3’UTR of c-MYC is likely to be superior to these therapies in pan cancers driven by c-MYC.
Citation Format: Chidiebere U. Awah. Pan cancer therapeutic inhibition of oncogenic c-MYC by the engineered destabilized 3’UTR of c-MYC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3039.