bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2638: The BCAR3/Cas/c-Src signaling node in breast cancer progression.
Authors: Batties Allison M. , Guerrero Michael S. , Wilson Ashley L. , Thomas Keena S. , Bouton Amy H. 
Published: August 2014

Abstract
Despite advances in early detection and improved adjuvant therapies, breast cancer remains the second leading cause of cancer death among women mainly due to metastatic spread of the disease. The ability of cancer cells to migrate and invade is important in the process of metastasis. Studies have shown that the adaptor protein Breast Cancer Antiestrogen Resistance 3 (BCAR3) is highly expressed in invasive breast cancer cell lines and functions as a positive regulator of migration and invasion. To date, BCAR3 has only one clearly established binding partner in breast cancer cells, the adaptor protein, p130Cas (Cas). Studies of human breast tumors have shown a positive correlation between high levels of Cas protein expression and poor clinical outcome in patients (Dorssers LC et al, 2004). Additionally, the protein tyrosine kinase c-Src is a C-terminal binding partner of Cas. c-Src kinase activity promotes enhanced Cas signaling and is associated with breast cancer progression and poor clinical outcome (Blscardi JS et al, 1999). These data suggest a critical role for the BCAR3/Cas/c-Src signaling node in breast tumor progression. We hypothesize that enhanced signaling through the BCAR3/Cas/c-Src network in breast epithelial cells is critical for the transition to an invasive cancer cell phenotype. In this work, we compared the relationship between these proteins in non-tumorigenic mammary epithelial cells (MCF10A) and invasive breast cancer cells (BT549 and MDA-MB-231). As is the case for invasive breast cancer cells, we found that the majority of BCAR3 in MCF10A breast epithelial cells is in complex with Cas. However, less Cas is found in association with c-Src in MCF10A cells compared to more invasive breast cancer cells. These finding suggest that despite some similarities in BCAR3, Cas, and c-Src signaling between non-tumorigenic and invasive breast cancer cells, both the physical interplay between these proteins and the signaling pathways activated downstream become dysregulated as non-tumorigenic cells progress to a fully oncogenic state. A better understanding of BCAR3/Cas/c-Src signaling in non-tumorigenic versus invasive breast tumor cells is necessary to determine whether this signaling network contributes to breast tumor progression and metastasis.
Citation Format: Allison M. Batties, Michael S. Guerrero, Ashley L. Wilson, Keena S. Thomas, Amy H. Bouton. The BCAR3/Cas/c-Src signaling node in breast cancer progression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2638. doi:10.1158/1538-7445.AM2013-2638
Abstract 2643: Regulation of stem cell differentiation by p53.
Authors: Li Mangmang , He Yunlong , Dubois Wendy , Huang Jing 
Published: August 2014

Abstract
Differentiation is one of the barriers for tumorigenesis and reprogramming. In addition, embryonic stem (ES) and induced pluripotent stem (iPS) cells utilize differentiation to maintain their genomic stability by removing cells with mutation burden from the population in response to DNA damage. The tumor suppressor p53 is critical for regulating the differentiation of ES and iPS cells. However, the mechanism of how p53 regulates the differentiation of ES and iPS cells is unclear. To systematically study the underlying mechanisms, we employ an integrated genome-wide study in mouse ES cells. Systems analyses reveal that p53-activated genes and p53-repressed genes have distinct regulatory mechanisms and functions in mouse ES cells. Binding of p53 at promoter region significantly correlates with gene activation but not with repression. In addition, we unexpectedly identify a novel regulatory mode for p53-mediated repression through interfering with distal enhancer activity. This regulatory mode explains some but not all of the p53-mediated repressive events. Importantly, many ES cell-enriched core transcription factors are p53-repressed genes. Further analyses demonstrate that p53-repressed genes are functionally associated with ES and iPS cell status while p53-activated genes are linked to differentiation. Genome-wide analyses also show that p53-activated genes and -repressed genes have distinguishable features of expression levels and epigenetic markers, such as H3K4me3, H3K27me3 and H3K79me2. Upon DNA damage, p53 regulates the self-renewal and pluripotency of ES cells. Together, these results support a model that, in response to DNA damage, p53 affects the status of ES cells through activating differentiation-associated genes and repressing ES cell-enriched genes. Because many poorly differentiated tumors express ES-cell gene signature, our results may also have far-reaching implications in how p53 restricts the origin of cancer stem cells in adult tissues.
Citation Format: Mangmang Li, Yunlong He, Wendy Dubois, Jing Huang. Regulation of stem cell differentiation by p53. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2643. doi:10.1158/1538-7445.AM2013-2643
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 2648: Self-renewing cellular compartments in embryonal rhabdomyosarcoma are modulated by Hedgehog signaling.
Authors: Satheesha Sampoorna , Dogan Nurhak , Casanova Elisa A. , Walter Dagmar , Schäfer Beat W. 
Published: August 2014

Abstract
Rhabdomyosarcoma (RMS) is a heterogeneous group of malignancies with features of impaired skeletal muscle differentiation and represents the majority of the soft tissue cancers in the pediatric age group. Current treatment regimens offer some clinical respite but at a significant risk of averse side effects and secondary tumors later in life. Identifying and targeting sub-populations with higher tumorigenic potential and self renewal capacity not only decreases tumor burden but also lowers the probability of relapse.
Using the sphere formation assay we could select for self-renewing cells from the heterogeneous monolayer cultures of embryonal RMS (eRMS) cell lines, RD and Rh36, which had multipotent differentiation ability in vitro and greater tumorigenic potential in vivo. These cells also showed increased expression of embryonic stem cell genes. Interestingly, quantitative gene expression analysis revealed increased expression of various components of the Hedgehog pathway, a developmental pathway important in eRMS biology. Inhibition or activation of the pathway in vitro by small molecule agents led to increased or decreased self renewing ability respectively. Furthermore we observed that eRMS adherent monolayer cultures contained a sub-population of GLI1-positive cells which could be modulated by pathway manipulation. Importantly, inhibition of the hedgehog pathway in vitro led to significantly delayed tumor initiation in vivo. Ongoing experiments aim at confirming these results on the genetic level.
We postulate that the Hedgehog pathway sustains a primitive cellular compartment necessary for tumor initiation within embryonal RMS cell lines.
Citation Format: Sampoorna Satheesha, Nurhak Dogan, Elisa A. Casanova, Dagmar Walter, Beat W. Schäfer. Self-renewing cellular compartments in embryonal rhabdomyosarcoma are modulated by Hedgehog signaling. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2648. doi:10.1158/1538-7445.AM2013-2648
Abstract 2649: Human adipose tissue-derived mesenchymal stem cells can target brain tumor initiating cells.
Authors: Choi Seung Ah , Wang Kyu-Chang , Phi Ji Hoon , Lee Ji Yeoun , Choi Jung Won , Kim Hyung Ah , Kim Se Hee , Kim Yong Hwy , Kwon Sung Eun , Kim Young-Hoon , Kim Seung-Ki 
Published: August 2014

Abstract
Abstract
The discovery of neural stem cells offers paradigm shift in brain tumor research. In neuro-oncology, the biology of neural stem cells has been pursued in two ways: as cancer stem cells to understand the origin and maintenance of brain tumors and as a potential cell-based vehicle for gene therapy. In addition to neural stem cells, mesenchymal stem cells (MSCs) have been reported to possess tumor-tropic migratory capacities. However, there is scanty data on migratory capacity of MSC toward brain tumor initiating cells (BTICs). This study focuses on investigating the ability of human adipose tissue derived MSCs (hAT-MSCs) to target BTICs and their cross-talk in the microenvironment.
BTICs were isolated from three different kinds of brain tumors (medulloblastoma, atypical teratoid/rhabdoid tumor (ATRT), glioblastoma). The migration capacities of hAT-MSCs toward BTICs were examined both in vitro transwell assay and in vivo bioluminescence imaging analysis. To investigate the crosstalk between hAT-MSCs and BTICs, various cytokines were analyzed. Using co-culture system of hAT-MSCs and BTICs, we analyzed the mRNA expression patterns of cytokine receptors (CCR2, CCR4, CCR5, CCR7, CCR9, CCR10, XCR1, CXCR1, IL-8R, CXCR4, CX3CR1, IL1R1, IL6R, MET, PDGFRB, KDR, CD44, IFNAR1 and TEK) by qRT-PCR and protein level of their ligand in co-cultured media by Bio-Plex human cytokine ELISA.
We confirmed the migratory capacity of t hAT-MSCs toward BTICs in vitro and BTICs-derived xenograft brain tumors in vivo live imaging. mRNA expression of receptors (CCR4, CCR5, CCR10, XCR1, CXCR1, IL-8R, CXCR4, PDGFRB, KDR, CD44, IFNAR1 and TEK) increased two- to eighteen-fold higher levels. The cytokine analysis revealed that the ligand levels of hAT-MSCs (medulloblastoma: VEGF, IL6, IL8, CCL3, CCL2 and TEK; ATRT: VEGF, CCL3 and TEK; glioblastoma: CCL2, PDGF, TEK and IGF1) and the ligand levels BTICs (medulloblastoma: CCL5 and CXCL4; ATRT: IL-8 and CXCL4; glioblastoma: CXCL4 and IGF1) were elevated in the co-cultured media.
Our findings demonstrated that hAT-MSCs can target BTICs. Cross-talk between hAT-MSCs cytokine receptor and BTICs ligand (medulloblastoma: CCR5/CCL5 and CXCR4/CXCL4; ATRT: IL-8R/IL-8 and CXCR4/CXCL4; glioblastoma: CXCR4/CXCL4 and IGF1R/IGF1) play cardinal role in this process.
Citation Format: Seung Ah Choi, Kyu-Chang Wang, Ji Hoon Phi, Ji Yeoun Lee, Jung Won Choi, Hyung Ah Kim, Se Hee Kim, Yong Hwy Kim, Sung Eun Kwon, Young-Hoon Kim, Seung-Ki Kim. Human adipose tissue-derived mesenchymal stem cells can target brain tumor initiating cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2649. doi:10.1158/1538-7445.AM2013-2649
Abstract 267: MYC maintains the self-renewal of cancer stem cells through the regulation of the glutathione redox system.
Authors: Das Bikul , Tsuchida Rika , Bayat-Mokhtari Reza , Gotlib Jason R. , Reijo-Pera Renee , Yeger Herman , Dean Felsher W. 
Published: August 2014

Abstract
Cancer stem cells (CSCs) are a rare population of self-renewing cells that can persist even after extensive therapeutic intervention. The molecular mechanism of CSC self-renewal is not yet clear. Here we show that MYC is causally involved in CSC self-renewal through the regulation of glutathione (GSH) redox system. In a MYC-driven conditional transgenic mouse model of T-cell acute lymphoblastic leukemia (T-ALL), we identified Sca-1+ CSCs. We found that these CSCs express the glutathione (GSH) redox system related genes including glutamate cysteine ligase (GCL) and Pyruvate Dehydrogenase Kinase 1 (PDK1) but low levels of expression of the mitochondrial redox enzyme, Superoxide Dismutase 2 (SOD2). Even a brief period of MYC inactivation in the Sca1+ CSCs led to their apoptosis associated with the downregulation of GCL and PDK1, but the upregulation of SOD2, in turn resulting in ROS-generation and mitochondrial damage. Moreover, suppression of SOD2 by siRNA silencing or the use of the peroxide scavenger, ascorbic acid, prevented MYC inactivation from inducing apoptosis in the Sca-1+ CSCs. Finally, in human CSCs, including primary human Chronic Myeloid Leukemia (CML), and human colon cancers, we confirmed that MYC expression was required for high GCL, PDK1 and low SOD2. Even the brief inactivation of MYC in human CSCs resulted in the loss of their self-renewal, as well as the global chance in redox state by decrease in GCL, PDK1 and increase in SOD2. We conclude that high levels of continued MYC expression are essential for CSC self-renewal through regulation of redox state.
Citation Format: Bikul Das, Rika Tsuchida, Reza Bayat-Mokhtari, Jason R. Gotlib, Renee Reijo-Pera, Herman Yeger, Felsher W. Dean. MYC maintains the self-renewal of cancer stem cells through the regulation of the glutathione redox system. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 267. doi:10.1158/1538-7445.AM2013-267
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 2685: Regulation of melanoma metastasis by malignant melanoma-initiating cell marker ABCB5.
Authors: Ma Jie , Alloo Allireza , Wilson Brian J. , Frank Markus H. 
Published: August 2014

Abstract
Cancer stem cells drive tumor growth, including metastatic disease progression. ATP-binding cassette member B5 (ABCB5) expression identifies malignant melanoma initiating cells (MMICs), which are distinguishable from cancer bulk populations by their self-renewal and differentiation capacities, and pro-oncogenic interactions with the microenvironment. ABCB5 confers drug resistance in multiple human malignancies through its actions as a drug efflux transporter. Here, we demonstrate that ABCB5 also regulates melanoma metastasis. ABCB5 monoclonal antibody (mAb) treatment significantly inhibited metastasis development in highly immune-compromised NOD-scid IL2Rγnull mice carrying fully established human melanoma xenografts, independent of previously reported antibody-dependent cell-mediated cytotoxicity (ADCC) effects. ABCB5 mAb treatment was well tolerated, as indicated by equal body weights of treated mice and untreated controls. Moreover, ABCB5 mAb also inhibited melanoma cell invasive capacity, suggesting that ABCB5 regulates intravasation and/or extravasation of metastatic tumor cells. Furthermore, the average size of metastatic nodules in ABCB5 mAb-treated mice was significantly smaller than those in isotype control mAb-treated or untreated mice, indicating that ABCB5 also regulates proliferation of disseminated tumor cells. Expression profile analysis revealed that multiple known metastasis-associated genes are regulated by ABCB5. Rescue of their expression could reverse the anti-metastatic effects induced by ABCB5 inhibition. Thus, ABCB5 is not only a marker for MMICs, but functionally drives metastatic melanoma progression.
Citation Format: Jie Ma, Allireza Alloo, Brian J. Wilson, Markus H. Frank. Regulation of melanoma metastasis by malignant melanoma-initiating cell marker ABCB5. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2685. doi:10.1158/1538-7445.AM2013-2685
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 2687: Krüppel-like factor 8 targets matrix metalloproteinase-14 to promote breast cancer invasion and metastasis .
Authors: Lu Heng , Hu Liu , Yu Lin , Wang Xianhui , Shen Chao , Li Tianshu , Mukherjee Debarati , Lahiri Satadru , Wason Melissa , Zhao Jihe 
Published: August 2014

Abstract
Krüppel-like factor 8 (KLF8) regulates critical gene transcription and invasion events associated with cancer, including epithelial to mesenchymal transition (EMT) and extracellular matrix degradation. Here, we report a novel KLF8-to- matrix metalloproteinase-14 (MMP14) signaling that promotes human breast cancer cell EMT, invasion and metastasis. Cell-surface protein biotinylation and streptavidin pull-down showed that overexpression of KLF8 induced cell-surface accumulation of MMP14 in MCF-10A cells in a FAK-dependent manner, which was correlated with increased MMP14 activity and the ectodomain shedding of E-cadherin. On the other hand, knockdown of KLF8 in MDA-MB-231 cells reduced expression and activity of MMP14 on the cell surface. Promoter reporter assays and chromatin and oligonucleotide precipitations determined that KLF8 activated the human MMP14 gene promoter both directly and indirectly via beta-catenin. Importantly, Matrigel invasion assays showed that MMP14 was required for the KLF8-induced MCF-10A cell invasion in vitro. Experiments using nude mice demonstrated that MMP-14 overexpression downstream of KLF8 in the MDA-MB-231 cells makes a significant contribution to the invasion and angiogenesis in the local primary tumors and lung metastasis. Taken together, this work identified a novel role and mechanisms for MMP14 downstream of KLF8 in the progression of breast cancer metastasis.
Citation Format: Heng Lu, Liu Hu, Lin Yu, Xianhui Wang, Chao Shen, Tianshu Li, Debarati Mukherjee, Satadru Lahiri, Melissa Wason, Jihe Zhao. Krüppel-like factor 8 targets matrix metalloproteinase-14 to promote breast cancer invasion and metastasis . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2687. doi:10.1158/1538-7445.AM2013-2687
Abstract 2694: SRC-1 promotes tumor angiogenesis through up-regulation of HIF1α-mediated VEGFa expression.
Authors: Qin Li , Xu Yixiang , Feng Zhen , Wu Yelin , Xu Yan , Liao Lan , Xu Jianming 
Published: August 2014

Abstract
Steroid receptor coactivator 1 (SRC-1) belongs to the p160 coactivator family which also contains SRC-2 (TIF2) and SRC-3 (AIB1/pCIP/ACTR/RAC3). These coactivators interact with nuclear receptors and other transcription factors to up-regulate gene expression. Accumulated evidence shows that SRC-1 exerts its promotive role in breast cancer progression and metastasis by up-regulating transcription of multiple genes important for tumor cell epithelial-mesenchymal transition (EMT), migration, invasion and endocrine therapy resistance. However, its role in tumor angiogenesis has not been examined. In our recent studies using SRC-1 KO/PyMT and WT/PyMT mammary tumor cell lines established in our lab, we found that injection of SRC-1 KO/PyMT cells to matrigel plug formed under the back skin in SCID mice induced less blood vessel formation compared with that of WT/PyMT tumor cells. Accordingly, injection of human breast cancer MDA-MB-231 cells with stable knockdown of SRC-1 by shRNA to the matrigel plug also induced less neovascularization. Meanwhile, VEGFa mRNA level is significantly reduced in mammary tumors from SRC-1 KO/PyMT transgenic mice. On the contrary, in SRC-1-overexpressed mammary tumors from MMTV/TVA/PyMT mice, the expression of VEGFa was dramatically increased. In agreement with these findings, in vitro studies revealed that VEGFa mRNA levels are much lower in two of the SRC-1 KO/PyMT tumor cell lines compared with WT/PyMT cell lines. Knockdown of SRC-1 in WT/PyMT cells and human MDA-MB-231 cells reduced VEGFa levels, while adenovirus-mediated re-expression of SRC-1 in SRC-1 KO/PyMT cells significantly potentiated VEGFa expression. Furthermore, promoter analyze revealed that SRC-1 could interact with HIF-1α and AP-1 to potentiate the VEGFa promoter activity. We also found that both SRC-1 and HIF-1α are associated with a VEGFa promoter region by ChIP assays. These results indicate that SRC-1 can promote breast cancer progression and metastasis through enhancing tumor angiogenesis. Targeting SRC-1 may be a feasible strategy for inhibiting breast tumor angiogenesis and metastasis.
Citation Format: Li Qin, Yixiang Xu, Zhen Feng, Yelin Wu, Yan Xu, Lan Liao, Jianming Xu. SRC-1 promotes tumor angiogenesis through up-regulation of HIF1α-mediated VEGFa expression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2694. doi:10.1158/1538-7445.AM2013-2694
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 2696: TMPRSS4 regulates levels of integrin alpha-5 in NSCLC through miR-205 activity.
Authors: Larzabal Leyre , Redrado Miriam , Lopez de Aberasturi Arrate , Rueda Paloma , Rodriguez Maria J. , Lopez Lissette , Montuenga Luis , Calvo Alfonso 
Published: August 2014

Abstract
TMPRSS4 is a membrane-anchored protease involved in cell migration and invasion in different cancer types including lung cancer. We have previously shown that TMPRSS4 expression is increased in NSCLC and that its inhibition through shRNA reduces lung metastasis. The goal of the present study was to elucidate molecular mechanisms involved in the protumorigenic role of TMPRSS4 in NSCLC. A knock down strategy and microarray analyses were established to identify genes regulated by TMPRSS4. Among other genes, miR-205 was identified as an overexpressed gene upon TMPRSS4 downregulation. Levels of miR-205 were found to be reduced in NSCLC cells compared to non-malignant cells. miR-205 overexpression promoted the acquisition of an epithelial phenotype with increased E-cadherin and reduced fibronectin expression, probably through the regulation of transcription factors ZEB1 and ZEB2. Furthermore, miR-205 inhibited very significantly (p&lt;0.01) tumor cell migration, invasion and metastasis formation in vivo. A further transcriptional and luciferase assays in miR-205-overexpressing cells identified integrin alpha-5 (a proinvasive protein overexpressed in tumors) as a new miR-205 target in NSCLC. We have therefore demonstrated for the first time a new molecular connection between TMPRSS4 and integrin alpha-5 through miR-205.
Citation Format: Leyre Larzabal, Miriam Redrado, Arrate Lopez de Aberasturi, Paloma Rueda, Maria J. Rodriguez, Lissette Lopez, Luis Montuenga, Alfonso Calvo. TMPRSS4 regulates levels of integrin alpha-5 in NSCLC through miR-205 activity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2696. doi:10.1158/1538-7445.AM2013-2696