bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-01-12: Detection of circulating cancer stem cells: A novel approach as a predictive marker for breast cancer metastases. This may be especially useful in patients with undetectable circulating epithelial tumor cells
Authors: Pizon M , Schott D , Pachmann U , Pachmann K 
Published: May 2019

Abstract
Background: Breast cancer is one of the most common types of cancer in women worldwide. It has been demonstrated that even localized tumors without clinically apparent metastases give rise to circulating epithelial tumor cells (CETCs). Recent studies have provided strong support for the circulating cancer stem cell (cCSC) hypothesis, which suggests that a more aggressive subpopulation of circulating tumor cells are the source of metastatic spread from the primary tumor. Measuring CETCs in blood of patients has emerged as a non-invasive diagnostic procedure for screening patients who may be at high risk for developing metastatic cancers. However, accurate detection of CETCs may provide erroneous results, since CETCs undergoing EMT during metastasis are down-regulated for the expression of epithelial cell markers.
Methods: 26 breast cancer patients were included into the study. The determination of CETCs and cCSC was performed using maintrac® method and tumorsphere forming assay, respectively. Cell viability, surface marker expression and ALDH 1 activity of the cells in the spheres were evaluated by fluorescence scanning microscope.
Results: Sphere formation was observed in 80 % of patients. We found that the number of tumorspheres depended on stage of disease. The number of tumorspheres increased significantly with tumor progression, especially with the presence of metastases. Tumorsphere formation was observed in all metastatic patients (median of 30 tumorspheres/100μl of blood), although only 27% of them had detectable CETCs. Analysis of surface marker expression profile showed that the cells in the spheres had typical phenotype of cancer stem cells. Sphere formation was not observed in healthy subjects (n=20).
Conclusion: There is a high correlation between the numbers of tumorspheres cultured from peripheral blood with clinical stage of disease. This may be an indicator of tumor aggressiveness, especially presence of metastases and may provide clinically useful prognostic information.
Citation Format: Pizon M, Schott D, Pachmann U, Pachmann K. Detection of circulating cancer stem cells: A novel approach as a predictive marker for breast cancer metastases. This may be especially useful in patients with undetectable circulating epithelial tumor cells [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-01-12.
Abstract P2-01-16: CRISPR-Cas9 screen identifies TMEM106A as a suppressor of breast cancer metastasis
Authors: Yang L , Yu S-J , Shao Z-M 
Published: May 2019

Abstract
Purpose: Breast cancer is one of the most common malignancies among women. The majority of cancer-associated deaths are caused by metastasis. Many biological alterations occur during this complex process, including the epithelial-mesenchymal transition (EMT), tumor immune escape, transendothelial migration (TEM). However, the biological mechanism of metastatic disease remains poorly understood and more need to be done to unify our understanding of underpinnings for metastasis in breast cancer.
Methods: We performed functional screening with CRISPR-Cas9 Genome-Scale CRISPR Knock-Out (GeCKO) library to identify metastasis-associated genes in breast cancer. We confirmed the function of a set of genes by transwell assays to testify the efficacy of in vivo screening. Further, we conducted in vitro and in vivo assays to explore the mechanism of TMEM106A in suppressing metastasis of breast cancer.
Results: The CRISPR-Cas9 library screening identified genes with potential of suppressing metastasis in breast cancer. Further validation of COPS2, SSBP2, TDG, DYRK4, GSG1, TMEM106A and PRR5L revealed that knock down of these genes promoted cell migration and invasion ability. In MDA-MB-231 and MDA-MB-468 cells, knock down of TMEM106A promoted in vitro migration, invasion, wound healing and in vivo pro-metastasis ability. In addition, E-cadherin was down-regulated and N-cadherin was up-regulated with suppression of TMEM106A. Accordingly, the potentiality of pro-metastasis was reversed when exogenous TMEM106A was expressed in MDA-MB-231 and MDA-MB-468 cells. We found the interaction between TMEM106A and WDR77 via Co-IP and MS analysis. Down-regulation of TMEM106A promoted expression of WDR77, which primarily occurred in the cytoplasm. To verify the association between TMEM106A and WDR77, we interfere WDR77 expression in MDA-MB-231 sg-TMEM106A, and the pro-metastasis effect of TMEM106A down-regulation was reversed.
Discussion: CRISPR-Cas9 library screening is an effective strategy to identify genes associated with breast cancer metastasis. The positive selection provides us a set of genes with potentiality to repress migration and invasion. TMEM106A may suppress metastasis via influencing translocation of WDR77 in breast cancer.
Citation Format: Yang L, Yu S-J, Shao Z-M. CRISPR-Cas9 screen identifies TMEM106A as a suppressor of breast cancer metastasis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-01-16.
Abstract P2-01-21: Not presented
Authors: Hyder SM , Cook MT , Liang Y 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Hyder SM, Cook MT, Liang Y. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-01-21.
Abstract P2-01-23: Not presented
Authors: Xing W , Li Q , Cao R , Sun G , Jiang C 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Xing W, Li Q, Cao R, Sun G, Jiang C. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-01-23.
Abstract P2-01-24: Sulindac and triple negative breast cancer progression
Authors: Xi Y , Yi B , Riker A 
Published: May 2019

Abstract
In 2018, a total of 266,120 new cases and 40,920 deaths from breast cancer in the United States were estimated by the American Cancer Society. Breast cancer is the most common malignancy and the second leading cause of death among American women. In this study, we will focus on triple negative breast cancer (TNBC), which is viewed by oncologists as a problematic and unpredictable sub-category of breast cancer because of higher rates of recurrence and poorer prognosis. TNBC accounts for up to 20% of all breast cancers and is highly prevalent in minority and young women. On average, 70% of women with metastatic TNBC die within 5 years, regardless of chemotherapy or other treatments. As such, there is an urgent medical need to develop more effective drugs to manage this deadly disease that already raised a health disparity concern, especially in the State of Louisiana. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used drugs for the treatment of pain, fever, and inflammation. Epidemiological studies have reported that the long term use of NSAIDs can prevent the occurrence multiple types of cancers, including breast cancer. However, their long term use for chemoprevention is not recommended because of toxicities associated with cyclooxygenase (COX) inhibition and the suppression of physiologically important prostaglandins. Our results show that the NSAID, sulindac sulfide (SS) and its non-COX inhibitory derivatives, can significantly inhibit the growth of the major subtypes of TNBC cells (basal-like, mesenchymal, and luminal). In addition, the compounds significantly inhibit tumor cell invasion. The animal experiments using Patient Derived Xenograft models supported the in vivo efficacy of these drugs. While studying the mechanism, we found that four oncogenic miRNAs, miR-10b, miR-17, miR-21, and miR-9 can be downregulated by SS and derivatives, and they were reported to promote tumor metastasis exclusively. Therefore, we conclude that those oncogenic miRNAs are involved in anti-metastatic activities of SS and its new non-COX inhibitory derivatives in TNBC.
Citation Format: Xi Y, Yi B, Riker A. Sulindac and triple negative breast cancer progression [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-01-24.
Abstract P2-02-02: The receptor tyrosine kinase EphA2 promotes glutamine metabolism in tumors by activating the transcriptional coactivators YAP and TAZ
Authors: Edwards DN , Ngwa VM , Wang S , Shiuan E , Brantley-Sieders DM , Kim LC , Reynolds AB , Chen J 
Published: May 2019

Abstract
Malignant tumors reprogram cellular metabolism to support cancer cell proliferation and survival. Although most cancers depend on a high rate of aerobic glycolysis, many cancer cells also display addiction to glutamine. Glutamine transporters and glutaminase activity are critical for glutamine metabolism in tumor cells, and upstream regulatory signaling pathways may represent a novel mechanism for targeted therapies in glutamine-addicted breast tumors such as Her2-overexpressing and triple-negative breast cancers (TNBC). We have found that the receptor tyrosine kinase EphA2 activated the transcriptional coactivators YAP and TAZ (YAP/TAZ), likely in a ligand-independent manner, to promote glutamine metabolism in cells and mouse models of breast cancer. Overexpression of EphA2 induced the nuclear accumulation of YAP and TAZ and increased the expression of YAP/TAZ target genes. Inhibition of the GTPase Rho or the kinase ROCK abolished EphA2-dependent YAP/TAZ nuclear localization. Silencing YAP or TAZ reduced the amount of intracellular glutamate through decreased expression of SLC1A5 and GLS, respectively, genes that encode proteins that promote glutamine uptake and metabolism. The regulatory DNA elements of both SLC1A5 and GLS contain the consensus sequence of the TEAD family of transcription factors that are closely associated with YAP/TAZ and were bound by TEAD4 in an EphA2-dependent manner. In patient breast cancer tissues, EphA2 expression positively correlated with that of YAP and TAZ, as well as that of GLS and SLC1A5. Although high expression of EphA2 predicted enhanced metastatic potential and poor patient survival, it also rendered breast cancer cells more sensitive to glutaminase inhibition. The findings define a previously unknown mechanism of EphA2-mediated glutaminolysis through YAP/TAZ activation in breast cancer and identify potential therapeutic targets in patients.
Citation Format: Edwards DN, Ngwa VM, Wang S, Shiuan E, Brantley-Sieders DM, Kim LC, Reynolds AB, Chen J. The receptor tyrosine kinase EphA2 promotes glutamine metabolism in tumors by activating the transcriptional coactivators YAP and TAZ [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-02-02.
Abstract P2-02-07: Targeting iron metabolism in breast cancer: Ferroptosis and genome stability
Authors: Possemato RL , Sviderskiy VO , Alvarez SW , Terzi EM 
Published: May 2019

Abstract
Iron-sulfur clusters are cell-essential protein cofactors in at least 48 human enzymes supporting diverse cellular functions, including genomic integrity and oxidative phosphorylation, and acting as molecular sensors for oxygen and iron levels. We recently described that breast cancer cells are particularly dependent upon robust iron-sulfur cluster biosynthesis for the survival of elevated oxygen conditions, including seeding lung metastases (1). Moreover, we found that even partially blocking cluster synthesis activated an iron-starvation response, rendering breast cancer cells susceptible to oxidative stress and death by ferroptosis (1). However, the precise mechanisms underlying these phenotypes remain to be fully elucidated. Here, we find that basal-like breast cancer cells are particularly susceptible to suppression of iron-sulfur cluster biosynthesis. By systematically evaluating proteins containing iron-sulfur clusters, we discovered that this susceptibility lies in the intrinsic vulnerability of basal-like breast cancer cells to genomic instability. These results have enabled us to define specific molecular targets in basal-like breast cancer which induce DNA damage, replication fork instability, and apoptosis, with striking subtype specificity. Our findings have broad implications for the underlying differences in genomic integrity in basal-like and luminal breast cancer subsets, and will inform future novel strategies to target genomic integrity in basal-like breast cancer.
1. Alvarez S, Sviderskiy VO, Terzi EM, Papagiannakopoulos T, Moreira AL, Adams S, Sabatini DM, Birsoy K, and Possemato R. NFS1 Undergoes Positive Selection in Lung Tumors and Protects Cells From Elevated Oxygen Levels and Ferroptosis, Nature. 2017 Nov 30;551(7682):639-643.
This work was supported by a Susan G. Komen Career Catalyst Award and the NCI (R01 CA214948).
Citation Format: Possemato RL, Sviderskiy VO, Alvarez SW, Terzi EM. Targeting iron metabolism in breast cancer: Ferroptosis and genome stability [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-02-07.
Abstract P2-02-10: Progesterone receptor membrane component-1 interacts with proteins of the cholesterol synthesis pathway resulting in altered cholesterol metabolism in breast cancer cells: Potential mechanism contributing to breast cancer progression
Authors: Ludescher M , Stamm N , Niederacher D , Ruckhäberle E , Fehm T , Neubauer H 
Published: May 2019

Abstract
Background: Progesterone Receptor Membrane Component-1 (PGRMC1) is upregulated in breast tumors and elevated expression of PGRMC1 is associated with increased tumor growth, indicating that PGRMC1 plays a role in carcinogenesis of breast cancer. However, the mechanism by which PGRMC1 contributes to breast cancer progression is not understood yet. Here we describe a potential mechanism by which PGRMC1 contributes to progression of breast cancer via deregulation of cholesterol synthesis and metabolization.
Methods: PGRMC1 interaction partners were identified by co-immunoprecipitation followed by mass spectrometry and validated using proximity ligation assay (PLA) in various breast cancer cell lines. To study how elevated PGRMC1 expression contributes to cholesterol balance, we generated PGRMC1 overexpressing breast cancer cells and determined levels of cholesterol-, lathosterol- and the cholesterol metabolite 27-hydroxycholesterol. Since 27-hydroxycholesterol is presumed to have estrogenic action, stimulating the growth of ER-positive breast cancer cells and limiting the effectiveness of aromatase inhibitors, we further investigated the activity of ERα in PGRMC1 overexpressing cell lines.
Results: Interaction of PGRMC1 with proteins involved in cholesterol synthesis, including Acyl-CoA desaturase (SCD), Squalene synthase (FDFT1) and Lanosterol 14-alpha demethylase (CYP51A1), was detected by mass spectrometry and verified by PLA. Elevated levels of cholesterol and its metabolites were detected in PGRMC1 overexpressing cells, suggesting a contribution of PGRMC1 to cholesterol synthesis and metabolization. Further, increased activity of ERα was found in PGRMC1 overexpressing cells, indicating activation of the receptor by cholesterol metabolites.
Conclusion: Cholesterol metabolism is involved in cancer cell proliferation as well as resistance to anti-cancer therapy. Our results indicate that elevated cholesterol metabolism induced by interaction of PGRMC1 with enzymes of the cholesterol biosynthesis pathway might contribute to malignant transformation and promote breast cancer progression. PGRMC1 might therefore present an interesting target for anti-cancer therapy.
Citation Format: Ludescher M, Stamm N, Niederacher D, Ruckhäberle E, Fehm T, Neubauer H. Progesterone receptor membrane component-1 interacts with proteins of the cholesterol synthesis pathway resulting in altered cholesterol metabolism in breast cancer cells: Potential mechanism contributing to breast cancer progression [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-02-10.
Abstract P2-02-16: Not presented
Authors: Li Y , Chu J , Li J , Tang J , Yin Y 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Li Y, Chu J, Li J, Tang J, Yin Y. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-02-16.
Abstract P2-06-04: Enhancing abiraterone acetate efficacy in androgen receptor-positive triple negative breast cancer: Chk1 as a potential target
Authors: Grellety T , Callens C , Richard E , Pulido M , Goncalves A , Gestraud P , MacGrogan G , Bonnefoi H , Cardinaud B 
Published: May 2019

Abstract
Purpose: Our aim was to identify predictive factors of abiraterone acetate (AA) efficacy and putative new druggable targets in androgen receptor (AR)-positive triple-negative breast cancer (TNBC) treated in the UCBG 2012-1 trial.
Material and methods: We defined AA response as either complete or partial response, or stable disease at 6 months. Using Ampliseq, we sequenced 91 general and breast cancerassociated genes from the tumor DNA samples. We analyzed transcriptomes from the extracted RNA samples on a Nanostring platform and performed immunohistochemistry (IHC) on tumor samples using tissue microarrays. We assessed AA and CHK1 inhibitors (GDC-0575 and AZD7762) efficacies, either alone or in combination, on cell lines grown in vitro and in vivo.
Results: Classical IHC apocrine markers, including AR, FOXA1, GGT1 and GCDFP15, allowed identifying AA responders and non-responders. All responders have clear apocrine features. Transcriptome analysis revealed that 31 genes were differentially expressed in the two subgroups, 9 of them being linked to proliferation and DNA damage repair. One of the most significant differences was the overexpression in non-responders of CHEK1, a gene encoding Chk1, a protein kinase that can be blocked by specific inhibitors. In vitro, AA and Chk1 inhibitor combination showed additive or slightly synergistic effect on cell viability, cell cycle, apoptosis and accumulation of DNA damages. In vivo, orthotopic xenograft experiments confirmed the efficacy of this combination therapy.
Conclusions: This study suggests that apocrine features can be helpful in the identification of AA-responders. We identified Chk1 as a putative drug target in AR-positive TNBCs.
Citation Format: Grellety T, Callens C, Richard E, Pulido M, Goncalves A, Gestraud P, MacGrogan G, Bonnefoi H, Cardinaud B. Enhancing abiraterone acetate efficacy in androgen receptor-positive triple negative breast cancer: Chk1 as a potential target [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-06-04.
Abstract P2-06-14: The role of SLC7A5 (LAT1) in endocrine therapy-resistant breast cancer
Authors: Sevigny CM , Sengupta S , Luo Z , Jin L , Pearce D , Clarke R 
Published: May 2019

Abstract
Endocrine therapies are commonly used to treat estrogen receptor-positive (ER+) breast cancers, which comprise 70% of all new breast cancer cases. Unfortunately, emergence of resistance to these therapies presents a major clinical challenge. Cancer cells can adapt to the dysregulation of cellular metabolism induced by endocrine therapy in order to evade cell death.Central to this adaptation is the scavenging of free-formed amino acids from the tumor microenvironment. For example, we found 109 solute carrier (SLC) mRNAs to be differentially expressed between endocrine-sensitive and resistant cells. We began our mechanistic studies of these genes with SLC family 7 member 5 (SLC7A5 or LAT1). SLC7A5 is a key component of a transmembrane transporter, which can complex with CD98 and increase the uptake of large, neutral amino acids (such as leucine or tyrosine).
We used a panel of endocrine therapy-resistant (LCC9) and sensitive (MCF7; LCC1) breast cancer cells. SLC7A5 expression was upregulated by estrogen in MCF7 and LCC1 cells; this induction was blocked by fulvestrant treatment. Basal expression of the SLC7A5 protein in the absence of estrogen was 2.75-fold higher in LCC9 cells compared with MCF7 cells; SLC7A5 mRNA expression was 71-fold higher. Fulvestrant treatment did not significantly alter SLC7A5 mRNA or protein expression in LCC9 cells. Inhibiting SLC7A5 function using either a pharmacological inhibitor (JPH203), or depleting expression using siRNA, led to significant suppression of LCC9 cell growth. Cell cycle analysis revealed that SLC7A5 depletion caused cells to accumulate in the G1-phase, with a concurrent reduction of cells in S-phase. In four publicly available datasets of ER+, tamoxifen treated breast cancer patients, high expression of SLC7A5 was significantly associated with poor relapse-free survival.
This study uncovers a novel adaptive mechanism in endocrine therapy-resistant breast cancer cells that is facilitated by increased expression of SLC7A5, which enables them to supplement their increased metabolic needs and promoting cell growth. Blocking the functions of SLC7A5, perhaps in conjunction with inhibition of autophagy, may therefore offer a new avenue of potential therapeutic intervention against endocrine therapy-resistant breast cancers.
Citation Format: Sevigny CM, Sengupta S, Luo Z, Jin L, Pearce D, Clarke R. The role of SLC7A5 (LAT1) in endocrine therapy-resistant breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-06-14.