bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-284: Retinoblastoma tumor suppressor protein phosphorylation and inactivation depend on direct interaction with Pin1
Authors: Rizzolio Flavio , Lucchetti Chiara , Caligiuri Isabella , Marchesi Irene , Caputo Mariella , Toffoli Giuseppe , Szanto Andres J. , Bagella Luigi , Castronovo Matteo , Giordano Antonio 
Published: August 2012

Abstract
It is well known that alterations in the pathway controlling pRb phosphorylation account for more than 50% of tumors. Here, we report a striking experimental demonstration that, in cancer cells, pRb phosphorylation by CDK/cyclin proteins depends on Pin1 activity. We propose, for the first time, a detailed mechanism regarding pRb phosphorylation and activity, thereby significantly advancing the basic understanding of cell cycle control. We conclude that at the beginning-middle of G1, CDKs phosphorylate pRb pocket domain, thus allowing its interaction with Pin1. Next, in mid-late G1, the new complex pRb-Pin1 allows CDKs to complete pRb phosphorylation, and therefore allows the expression of S phase entry genes (Cell Death & Differentiation, in press). We believe our finding will have broad implications on target therapy for cancer patients. In fact, cancer cells can inactive pRb by overexpressing only Pin1, without affecting the well-known CDK pathways. Since Pin1 is overexpressed in most tumors, this suggests a new approach to treating cancer patients by utilizing Pin1 inhibitors in combination with or without CDK inhibitors.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-284. doi:1538-7445.AM2012-LB-284
Abstract LB-285: Regulation of therapy resistance in slow-cycling cancer cells
Authors: Moore Nathan , Chen Amy , Kamionek Michal , Houghton JeanMarie , Lyle Stephen 
Published: August 2012

Abstract
Tumor recurrence after chemotherapy is a major cause of patient morbidity and mortality. Recurrences are thought to be due in part to small subsets of cancer cells that are better able to survive traditional forms of chemotherapy and thus drive tumor re-growth. The ability to isolate and better characterize these therapy-resistant cells is critical for the future development of targeted therapies aimed at achieving more robust and long-lasting responses. Slow-cycling stem cells are integral components of adult epithelial tissues and are required for tissue maintenance. These slow-cycling cells are inherently resistant to traditional forms of chemotherapy that primarily target actively cycling cells. Using a novel application for the proliferation marker CFSE, we have identified populations of slow-cycling, label-retaining cells (LRCs) in primary tumors and cancer cell lines. As predicted, quiescent LRCs exhibit a multi-fold increase in chemoresistance but retain the ability to re-enter the cell cycle. We further demonstrate the innovative application of CFSE to live sort slow-cycling tumor cells and begin to explore the mechanisms behind LRC resistance and survival. Using RT-PCR and immunoblotting, we have observed consistent over-expression of the CDK5 activator, p35, in LRCs of both primary tumor xenografts and in-vitro sphere cultures. While p35 is known to play an active role in neurogenesis, cell migration, and apoptosis within the developing brain, its role in tumor biology remains unclear. Manipulation of p35 expression affects cell cycle distribution, extent of the LRC pool, and cell survival when challenged with traditional forms of chemotherapy. Additionally, we demonstrate that alterations in p35 expression alters downstream CDK5 signaling and the activation state of BCL2. Combined, our data suggest a model whereby the CDK5/p35 complex acts to slow cell cycling speed and change expression of BCL2, promoting resistance to chemotherapy. Future p35 targeting, in combination with traditional forms of chemotherapy, may help to reduce recurrence rates and increase long-term patient survival.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-285. doi:1538-7445.AM2012-LB-285
Abstract LB-291: Role of exosomes in tumor cell adhesion and survival
Authors: Koumangoye Rainelli B. 
Published: August 2012

Abstract
Exosomes are nanovesicles secreted by all living cells. These vesicles are abundant in serum and other extracellular fluids and contain a large repertoire of proteins, mRNA and microRNA. Exosomes have been implicated in cell to cell communication, the transfer of infectious agents, neurodegenerative diseases as well as tumor progression. However, the precise mechanisms by which they are internalized and/or secreted remain poorly understood. In order to follow their release and uptake in breast tumor cells in real time, cell-derived exosomes were tagged with green fluorescent protein (GFP)-CD63. Shown here for the first time is the demonstration that detachment of adherent cells from substratum induces a rapid and substantial secretion of exosomes which then concentrate on the cell surfaces and are re-internalized to mediate adhesion to various extracellular matrix molecules (ECM). In contrast, ECM-immobilized exosomes inhibited cell adhesion and spreading. Disruption of lipid rafts with methyl-beta-cyclodextrin (MβCD) inhibits the internalization of exosomes. Moreover, when short hairpin RNA techniques are used to knockdown lipid raft-interacting proteins AnxA2 and AnxA6, the resultant Anx-depleted breast carcinoma cell lines exhibited decreased exosomes uptake and decreased cellular adhesion. Non-transformed primary breast epithelial cells treated with exosomes induced rapid cell cycle progression, disorganized cellular masses and anoikis resistance in three-dimensional cell culture systems. These data indicate that exosomes contribute to both cancer cell adhesion and survival mechanisms.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-291. doi:1538-7445.AM2012-LB-291
Abstract LB-292: NANOG promotes chemoresistance in prostate carcinoma cells
Authors: Jiang Hongmei , Wang Man-Tzu , Nie Daotai 
Published: August 2012

Abstract
NANOG promotes chemoresistance in prostate carcinoma cells Hongmei Jiang, Man-Tzu Wang, Daotai Nie The emergence of drug resistant prostate cancer cells is a leading cause of chemotherapy failure in patients with prostate cancer. The mechanisms behind the acquisition of chemoresistance in prostate cancers are, however, poorly understood. NANOG is a transcription factor associated with the self-renewal of embryonic stem cells. Expression of NANOG has been detected in a number of cancer cells, and its expression linked with those positive for stem/progenitor markers. In the present studies, several lines of evidence are presented to suggest that NANOG regulates tumor responses to chemotherapy. First, in the surviving fractions of tumor cells after chemotherapy, there was an elevated level of NANOG expression and activities. Second, prospective enrichment of tumor cells with endogenous NANOG expression led to enrichment of tumor cells resistant to taxol, vinblastine, and doxorubicin. Knockdown of NANOG expression via small hairpin RNAs (shRNAs) sensitized tumor cells toward chemotherapeutics. Real-time PCR array identified an enhanced expression of the ATP-binding cassette efflux transporter B1 (ABCB1) and G2 (ABCG2) in tumor cells enriched with endogenous NANOG expression. Inhibition of ABCB1 activities or knockdown of ABCB1 expression attenuated, but not abolished, the increased resistance in NANOG expressing cells toward taxol and vinblastine. Knockdown of ABCG2 attenuated the resistance of NANOG-expressing tumor cells toward doxorubicin. Together, our results suggest that NANOG confers tumor cells with increased resistance to chemotherapy partially through regulating the expression of ABC transporters.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-292. doi:1538-7445.AM2012-LB-292
Abstract LB-296: Allikrein 14 induces epithelial-mesenchymal transition-like changes in colon cancer cells
Authors: Darmoul Dalila 
Published: August 2012

Abstract
Accumulating evidence indicates that serine proteinase family of the kallikrein-related-peptidases (KLK1-KLK15) are deregulated in cancer and their up-regulation is often associated with poor patient prognosis. Although primarily known as cancer biomarkers, recent evidence implicates KLKs in many cancer-related processes, including cell-growth, angiogenesis, invasion and metastasis. In addition, KLKs have emerged as signalling molecules by selectively targeting members of a unique subfamily of cell surface G-protein coupled receptors termed, proteinase-activated receptors (PARs). PARs are now considered important players in the development of human colon cancer. Indeed, we have previously demonstrated that in colonic tumours, upregulated PAR-2 and aberrantly expressed PAR-1 and PAR-4 control human colon cancer cell migration and proliferation. Recently, we showed that some members of the aberrantly expressed KLKs mediate these responses by signalling of through PARs. We hypothesized that KLK14 induced-cell migration and colonic tumour invasion are the consequence of epithelial-mesenchymal transition. We focused on KLK14 for which morphological changes were observed when colon cancer cells were treated with KLK14. We found that: 1) microscopic analysis showed redistribution of perijunctional F-actin in KLK14 treated HT29 cells, a colon cancer derived adenocarcinmoma; 2) HT29 cell treatment with KLK14 induced loss of E-cadherin-mediated cell-cell adhesion; 3) Biochemical studies showed down regulation of epithelial markers and upregulation of mesenchymal markers, the molecular mechanisms involved are under investigation. These results suggest for the first time that some KLKs are key mediators of induced ETM in human colonic tumors.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-296. doi:1538-7445.AM2012-LB-296
Abstract LB-298: EGF induces EMT through PI3K/Akt and MAPK singnaling pathways in breast cancer cell lines
Authors: Kim Jin Kyoung , Kong Jienan , Lee Youngseok , Jeong Hoiseon , Kim Aeree 
Published: August 2012

Abstract
EMT, epithelial-mesenchymal transition, is defined by the loss of epithelial characteristics and the acquisition of mesenchymal properties, such as reduced cell to cell contact, spindle morphology, expression mesenchymal markers and migratory function. In carcinogenesis, EMT is known to be associated with increased aggressiveness, and invasive and metastatic potential. Although various factor, such as EGF signaling pathways, cytokines, miRNAs, Wnt signaling and TGF-ß signaling have been suggested as inducers of EMT signaling pathway, detailed mechanism haven't been clarified except TGF-ß induced EMT. This study was designed to evaluate if and how EGF can induce EMT in breast cancer cell lines. We showed EGF induced EMT, such as elongation of cancer cells, down regulation of E-cadherin, and upregulation of vimentin and fibronectin in MCF-7 and MDA-MB-231 cell lines. In addition, we confirmed that EMT by EGF was induced via MAPK and PI3K/Akt signaling pathway using LY294002 (PI3K inhibitor) and PD98059 (MAPK inhibitor). PI3K inhibitor and MAPK inhibitor also blocked phosphorylation of Smad2 and inhibited nuclear localization of p-Smad2. With using SB203580 (p-Smad2 inhibitor) inhibited expression of Snail. In summary, EGF induces EMT through PI3K/Akt and MAPK signaling pathways, which activate downstream of Smad2 and Sanil signaling in MCF-7 and MDA-MB-231 cell lines.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-298. doi:1538-7445.AM2012-LB-298
Abstract LB-3: Evidence that dibenzofuran based anti-angiogenic, anti-tumor peptidomimetics target galectin-1
Authors: Dings Ruud P.M. , Miller Michelle C. , Kumar Nigam , Mayo Kevin H. 
Published: August 2012

Abstract
Galectins, named for their selective binding to ß-galactoside-containing glycans, play crucial roles in many physiological as well as pathological processes. Galectin-1 (gal-1) in particular, has been shown to be differentially elevated in tumor endothelial cells in several cancers including cancer of the breast, colon, prostate and ovaries. Gal-1 targeting 33mer peptide, Anginex, inhibits tumor endothelial cell proliferation via anoikis and attenuates tumor angiogenesis and tumor growth. Based on structure-activity relationships of anginex, partial-peptide mimetic were designed, using dibenzofuran (DBF) as a ß-turn mimetic to maintain the two key ß-strands and the bioactive amphipathic ß-sheet conformation of the peptide. The best DBF-based compound 6DBF7 (13mer) inhibited tumor angiogenesis and tumor growth in vivo better than parent anginex. Here we report on the optimization of the anti-angiogenic activity of 6DBF7 analogs in vitro, by substitution of natural and non-natural amino acids, and subsequently the antiangiogenic and anti-tumor effects of the most promising analogs in vivo. In addition, by using NMR spectroscopy and flow cytometry, we demonstrate that the lead 6DBF7 analogs interact with galectin-1 at a site near to its carbohydrate binding domain and by doing so can compete off galectin-1 from binding to ß-galactoside-containing glycans on the surface of cells in vitro. Overall, this research contributes to our ability to design pharmaceutical agents that target galectin-1 and thereby inhibit tumor growth and are potentially clinical candidates for use in the management of human cancers. This work was supported by NIH grant CA096090 to KHM
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-3. doi:1538-7445.AM2012-LB-3
Abstract LB-30: A functional analysis of the nuclear RhoGEF Ect2 in ovarian cancer
Authors: DeCristo Molly J. , Parker Lauren E. , Trembath Dimitri , Kuan Pei-Fen , Yim Margaret , Liu Jinsong , Miller C. Ryan , Der Channing J. , Cox Adrienne D. 
Published: August 2012

Abstract
Ect2 is a guanine nucleotide exchange factor (GEF) and activator of Rho family small GTPases. Ect2 regulates RhoA, Rac1, and Cdc42, thereby playing an important role in the control of cell proliferation, survival, and migration. Originally identified as an oncogene in vitro, the role of Ect2 in regulating migration makes it of particular interest in ovarian cancer, in which local invasion and ascites are prevalent. Notably, ECT2 is located on 3q26.1-3q26.2, the most frequent amplicon in ovarian cancer, and it has been found to be overexpressed at the mRNA level in ovarian tumors. We first explored the role of Ect2 in ovarian cancer by knocking it down using shRNA and assessing anchorage-independent growth and both random and directed migration in a panel of ovarian cancer cell lines. Our findings reveal that Ect2 expression is required for each of these functions. Interestingly, we found that Ect2 utilization of specific Rho GTPase substrates is highly context-dependent. In addition, to investigate the potential clinical importance of Ect2, we studied its expression and localization in primary epithelial ovarian cancers, using over 300 histological tumor and cyst samples incorporated into a tissue microarray (TMA). Ect2 is unusual among the RhoGEFs because of its localization. A critical regulator of cytokinesis, it is sequestered to the nucleus in interphase cells. It has been hypothesized that the overexpression and mislocalization of Ect2 into the cytoplasm leads to aberrant Rho activation and oncogenesis. Unexpectedly, our recently completed TMA data analysis suggests that malignant serous ovarian cancer is instead associated with nuclear Ect2, while benign disease is associated with mislocalized, cytosolic Ect2. We are currently exploring a possible nuclear mechanism to explain these findings. Although standard immunohistochemical analyses typically report only total protein levels, our new data reveal that unrestricted subcellular localization of Ect2 is likely to be more important than total protein levels for ovarian pathology.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-30. doi:1538-7445.AM2012-LB-30
Abstract LB-427: TAK1 (MAP3K7) inhibition promotes apoptosis in KRAS dependent colon cancers
Authors: Singh Anurag , Sweeney Michael F. , Yu Min , Burger Alexa , Greninger Patricia , Benes Cyril , Haber Daniel A. , Settleman Jeff 
Published: August 2012

Abstract
Colon cancers frequently harbor KRAS mutations, yet only a subset of KRAS-mutant colon cancer cell lines are dependent upon KRAS signaling for survival. In a screen for kinases that promote survival of KRAS-dependent colon cancer cells, we found that the TAK1 kinase (MAP3K7) is required for tumor cell viability. The induction of apoptosis by RNAi-mediated depletion or pharmacologic inhibition of TAK1 is linked to its suppression of hyperactivated Wnt signaling, evident in both endogenous and genetically reconstituted cells. In APC-mutant/KRAS-dependent cells, KRAS stimulates BMP-7 secretion and BMP signaling, leading to TAK1 activation and enhancement of Wnt-dependent transcription. An in vitro-derived “TAK1-dependency signature” is enriched in primary human colon cancers with mutations in both APC and KRAS, suggesting potential clinical utility in stratifying patient populations. Together, these findings identify TAK1 inhibition as a potential therapeutic strategy for a treatment-refractory subset of colon cancers exhibiting aberrant KRAS and Wnt pathway activation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-427. doi:1538-7445.AM2012-LB-427
Abstract LB-44: Sister to sister
Authors: Whaley Lori A. 
Published: August 2012

Abstract
Mission Statement: To empower the minority community to take a more active role in meeting their health needs. Goals: To educate African American women & families about the importance of early detection of breast cancer, breast self-exam (BSE), clinical breast exam (CBE) and mammograms; to inspire and recruit survivors to participate in Women In Touch (WIT); to educate and gain the trust of minority women about enrolling in clinicals trials. Our Services: Wig bank, protheses, transportation, health care symposium, presentations at churches or civic groups, support group meetings, quarterly newsletters and financial assistance referrals.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-44. doi:1538-7445.AM2012-LB-44
Abstract LB-466: Genomic Loss of microRNA 491 contributes to IGFBP2 overexpression and stemness in GBM
Authors: Li Xia , Liu Yuexin , Ji Ping , Chua Yingxuan , Hu Limei , Guo Fei , Sun Yan , Lang Frederick , Zhang Wei 
Published: August 2012

Abstract
Insulin-like growth factor-binding protein 2 (IGFBP2) is overexpressed in 80% of glioblastoma multiforme (GBM, WHO grade IV). Our mouse model experiments demonstrated that IGFBP2 is a glioma oncogene. However, the underlying mechanism for overexpression of IGFBP2 remains unknown. We examined a total of 388 GBM samples from the Cancer Genome Atlas (TCGA) and found that miR-491, which is located on chr9p21.3, is deleted in 57% of cases. TargetScan analysis revealed that there is a binding site of miR-491 on the 3′-UTR of the IGFBP2 gene. The miR-491 expression levels in GBM patients are inversely correlated with that of IGFBP2. We validated this regulatory relationship by overexpression of miR-491 and observed down-regulation of IGFBP-2 in both protein level and mRNA level in U251 and T98G glioma cell lines. Conversely, miR-491 inhibitors increased IGFBP2 in LN229 cells which express low level of endogenous IGFBP2. Luciferase reporter assay further proved that IGFBP2 is a direct target of miR-491. Moreover, ectopic expression of miR-491 inhibited cell migration and invasion of U251 and T98G as efficiently as knockdown of IGFBP2 and such inhibitory effects can be partially reversed by overexpression of IGFBP2-EGFP in U251, supporting the notion that IGFBP2 plays an important role in miR-491's functions. To investigate the role of miR-491 in stemness of GBM, we introduced miR-491 into 3 patient-derived glioma stem cell lines and found that miR-49 downregulated CDK6 and Bcl-xL and inhibited neurosphere formation and cell proliferation. These findings suggest that miR-491 acts as a tumor suppressor miR by coordinately attenuating multiple oncogenes in GBM. Our results provide new insights into the mechanism for oncogenic IGFBP2 overexpression and may provide new opportunities for therapeutic strategies for GBM treatment.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-466. doi:1538-7445.AM2012-LB-466