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Article ; Online: Correction: 2'-Hydroxyflavanone effectively targets RLIP76-mediated drug transport and regulates critical signaling networks in breast cancer.

Nagaprashantha, Lokesh Dalasanur / Singhal, Jyotsana / Li, Hongzhi / Warden, Charles / Liu, Xueli / Horne, David / Awasthi, Sanjay / Salgia, Ravi / Singhal, Sharad S

Oncotarget

2022 Volume 13, Page(s) 331

Abstract: This corrects the article DOI: 10.18632/oncotarget.24720.]. ...

Abstract	[This corrects the article DOI: 10.18632/oncotarget.24720.].
Language	English
Publishing date	2022-02-11
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.28199
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Article ; Online: 2'-Hydroxyflavanone effectively targets RLIP76-mediated drug transport and regulates critical signaling networks in breast cancer.

Nagaprashantha, Lokesh Dalasanur / Singhal, Jyotsana / Li, Hongzhi / Warden, Charles / Liu, Xueli / Horne, David / Awasthi, Sanjay / Salgia, Ravi / Singhal, Sharad S

Oncotarget

2018 Volume 9, Issue 26, Page(s) 18053–18068

Abstract: Breast cancer (BC) is the most common cancer in women. Estrogen, epidermal growth factor receptor 2 (ERBB2, HER2), and oxidative stress represent critical mechanistic nodes associated with BC. RLIP76 is a major mercapturic acid pathway transporter whose ... ...

Abstract	Breast cancer (BC) is the most common cancer in women. Estrogen, epidermal growth factor receptor 2 (ERBB2, HER2), and oxidative stress represent critical mechanistic nodes associated with BC. RLIP76 is a major mercapturic acid pathway transporter whose expression is increased in BC. In the quest of a novel molecule with chemopreventive and chemotherapeutic potential, we evaluated the effects of 2'-Hydroxyflavanone (2HF) in BC. 2HF enhanced the inhibitory effects of RLIP76 depletion and also inhibited RLIP76-mediated doxorubicin transport in BC cells. RNA-sequencing revealed that 2HF induces strong reversal of the gene expression pattern in ER
Language	English
Publishing date	2018-04-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.24720
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Article ; Online: Oxidative stress and dietary phytochemicals: Role in cancer chemoprevention and treatment.

Chikara, Shireen / Nagaprashantha, Lokesh Dalasanur / Singhal, Jyotsana / Horne, David / Awasthi, Sanjay / Singhal, Sharad S

Cancer letters

2017 Volume 413, Page(s) 122–134

Abstract: Several epidemiological observations have shown an inverse relation between consumption of plant-based foods, rich in phytochemicals, and incidence of cancer. Phytochemicals, secondary plant metabolites, via their antioxidant property play a key role in ... ...

Abstract	Several epidemiological observations have shown an inverse relation between consumption of plant-based foods, rich in phytochemicals, and incidence of cancer. Phytochemicals, secondary plant metabolites, via their antioxidant property play a key role in cancer chemoprevention by suppressing oxidative stress-induced DNA damage. In addition, they modulate several oxidative stress-mediated signaling pathways through their anti-oxidant effects, and ultimately protect cells from undergoing molecular changes that trigger carcinogenesis. In several instances, however, the pro-oxidant property of these phytochemicals has been observed with respect to cancer treatment. Further, in vitro and in vivo studies show that several phytochemicals potentiate the efficacy of chemotherapeutic agents by exacerbating oxidative stress in cancer cells. Therefore, we reviewed multiple studies investigating the role of dietary phytochemicals such as, curcumin (turmeric), epigallocatechin gallate (EGCG; green tea), resveratrol (grapes), phenethyl isothiocyanate (PEITC), sulforaphane (cruciferous vegetables), hesperidin, quercetin and 2'-hydroxyflavanone (2HF; citrus fruits) in regulating oxidative stress and associated signaling pathways in the context of cancer chemoprevention and treatment.
MeSH term(s)	Animals ; Anticarcinogenic Agents/therapeutic use ; Antineoplastic Agents, Phytogenic/therapeutic use ; Antioxidants/therapeutic use ; Diet ; Drug Resistance, Neoplasm ; Humans ; Neoplasms/metabolism ; Neoplasms/pathology ; Neoplasms/prevention & control ; Oxidative Stress/drug effects ; Phytochemicals/therapeutic use ; Signal Transduction/drug effects
Chemical Substances	Anticarcinogenic Agents ; Antineoplastic Agents, Phytogenic ; Antioxidants ; Phytochemicals
Language	English
Publishing date	2017-11-04
Publishing country	Ireland
Document type	Journal Article ; Review ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	195674-7
ISSN	1872-7980 ; 0304-3835
ISSN (online)	1872-7980
ISSN	0304-3835
DOI	10.1016/j.canlet.2017.11.002
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Article ; Online: Translational opportunities for broad-spectrum natural phytochemicals and targeted agent combinations in breast cancer.

Dalasanur Nagaprashantha, Lokesh / Adhikari, Ramesh / Singhal, Jyotsana / Chikara, Shireen / Awasthi, Sanjay / Horne, David / Singhal, Sharad S

International journal of cancer

2017 Volume 142, Issue 4, Page(s) 658–670

Abstract: Breast cancer (BC) prevention and therapy in the context of life-style risk factors and biological drivers is a major focus of developmental therapeutics in oncology. Obesity, alcohol, chronic estrogen signaling and smoking have distinct BC precipitating ...

Abstract	Breast cancer (BC) prevention and therapy in the context of life-style risk factors and biological drivers is a major focus of developmental therapeutics in oncology. Obesity, alcohol, chronic estrogen signaling and smoking have distinct BC precipitating and facilitating effects that may act alone or in combination. A spectrum of signaling events including enhanced oxidative stress and changes in estrogen-receptor (ER)-dependent and -independent signaling drive the progression of BC. Breast tumors modulate ERα/ERβ ratio, upregulate proliferative pathways driven by ERα and HER2 with a parallel loss and/or downregulation of tumor suppressors such as TP53 and PTEN which together impact the efficacy of therapeutic strategies and frequently lead to emergence of drug resistance. Natural phytochemicals modulate oxidative stress, leptin, integrin, HER2, MAPK, ERK, Wnt/β-catenin and NFκB signaling along with regulating ERα and ERβ, thereby presenting unique opportunities for both primary and combinatorial interventions in BC. In this regard, this article focuses on critical analyses of the evidence from multiple studies on the efficacy of natural phytochemicals in BC. In addition, areas in which the combinations of such effective natural phytochemicals with approved and/or developing anticancer agents can be translationally beneficial are discussed to derive evidence-based inference for addressing challenges in BC control and therapy.
MeSH term(s)	Biomarkers, Tumor/antagonists & inhibitors ; Breast Neoplasms/metabolism ; Breast Neoplasms/prevention & control ; Drug Therapy, Combination ; Female ; Humans ; Molecular Targeted Therapy ; Phytochemicals/therapeutic use ; Translational Medical Research
Chemical Substances	Biomarkers, Tumor ; Phytochemicals
Language	English
Publishing date	2017-11-28
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	218257-9
ISSN	1097-0215 ; 0020-7136
ISSN (online)	1097-0215
ISSN	0020-7136
DOI	10.1002/ijc.31085
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Zs.A 478: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: RLIP76 regulates PI3K/Akt signaling and chemo-radiotherapy resistance in pancreatic cancer.

Kathryn Leake / Jyotsana Singhal / Lokesh Dalasanur Nagaprashantha / Sanjay Awasthi / Sharad S Singhal

PLoS ONE, Vol 7, Iss 4, p e

2012 Volume 34582

Abstract: Pancreatic cancer is an aggressive malignancy with characteristic metastatic course of disease and resistance to conventional chemo-radiotherapy. RLIP76 is a multi-functional cell membrane protein that functions as a major mercapturic acid pathway ... ...

Abstract	Pancreatic cancer is an aggressive malignancy with characteristic metastatic course of disease and resistance to conventional chemo-radiotherapy. RLIP76 is a multi-functional cell membrane protein that functions as a major mercapturic acid pathway transporter as well as key regulator of receptor-ligand complexes. In this regard, we investigated the significance of targeting RLIP76 on PI3K/Akt pathway and mechanisms regulating response to chemo-radiotherapy.Cell survival was assessed by MTT and colony forming assays. Cellular levels of proteins and phosphorylation was determined by Western blot analyses. The impact on apoptosis was determined by TUNEL assay. The anti-cancer effects of RLIP76 targeted interventions in vivo were determined using mice xenograft model of the pancreatic cancer. The regulation of doxorubicin transport and radiation sensitivity were determined by transport studies and colony forming assays, respectively.Our current studies reveal an encompassing model for the role of RLIP76 in regulating the levels of fundamental proteins like PI3K, Akt, E-cadherin, CDK4, Bcl2 and PCNA which are of specific importance in the signal transduction from critical upstream signaling cascades that determine the proliferation, apoptosis and differentiation of pancreatic cancer cells. RLIP76 depletion also caused marked and sustained regression of established human BxPC-3 pancreatic cancer tumors in nude mouse xenograft model. RLIP76 turned out to be a major regulator of drug transport along with contributing to the radiation resistance in pancreatic cancer.RLIP76 represents a mechanistically significant target for developing effective interventions in aggressive and refractory pancreatic cancers.
Keywords	Medicine ; R ; Science ; Q
Subject code	610 ; 500
Language	English
Publishing date	2012-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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Article ; Online: RLIP76 regulates PI3K/Akt signaling and chemo-radiotherapy resistance in pancreatic cancer.

Leake, Kathryn / Singhal, Jyotsana / Nagaprashantha, Lokesh Dalasanur / Awasthi, Sanjay / Singhal, Sharad S

PloS one

2012 Volume 7, Issue 4, Page(s) e34582

Abstract: Purpose: Pancreatic cancer is an aggressive malignancy with characteristic metastatic course of disease and resistance to conventional chemo-radiotherapy. RLIP76 is a multi-functional cell membrane protein that functions as a major mercapturic acid ... ...

Abstract	Purpose: Pancreatic cancer is an aggressive malignancy with characteristic metastatic course of disease and resistance to conventional chemo-radiotherapy. RLIP76 is a multi-functional cell membrane protein that functions as a major mercapturic acid pathway transporter as well as key regulator of receptor-ligand complexes. In this regard, we investigated the significance of targeting RLIP76 on PI3K/Akt pathway and mechanisms regulating response to chemo-radiotherapy. Research design and methods: Cell survival was assessed by MTT and colony forming assays. Cellular levels of proteins and phosphorylation was determined by Western blot analyses. The impact on apoptosis was determined by TUNEL assay. The anti-cancer effects of RLIP76 targeted interventions in vivo were determined using mice xenograft model of the pancreatic cancer. The regulation of doxorubicin transport and radiation sensitivity were determined by transport studies and colony forming assays, respectively. Results: Our current studies reveal an encompassing model for the role of RLIP76 in regulating the levels of fundamental proteins like PI3K, Akt, E-cadherin, CDK4, Bcl2 and PCNA which are of specific importance in the signal transduction from critical upstream signaling cascades that determine the proliferation, apoptosis and differentiation of pancreatic cancer cells. RLIP76 depletion also caused marked and sustained regression of established human BxPC-3 pancreatic cancer tumors in nude mouse xenograft model. RLIP76 turned out to be a major regulator of drug transport along with contributing to the radiation resistance in pancreatic cancer. Conclusions/significance: RLIP76 represents a mechanistically significant target for developing effective interventions in aggressive and refractory pancreatic cancers.
MeSH term(s)	Animals ; Apoptosis/drug effects ; Apoptosis/genetics ; Apoptosis/radiation effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Proliferation/radiation effects ; Cell Survival/drug effects ; Cell Survival/genetics ; Cell Survival/radiation effects ; Cell Transformation, Neoplastic ; Chemoradiotherapy ; Doxorubicin/metabolism ; Doxorubicin/pharmacology ; GTPase-Activating Proteins/deficiency ; GTPase-Activating Proteins/genetics ; GTPase-Activating Proteins/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Expression Regulation, Neoplastic/genetics ; Gene Expression Regulation, Neoplastic/radiation effects ; Gene Knockdown Techniques ; Humans ; Mice ; Pancreatic Neoplasms/metabolism ; Pancreatic Neoplasms/pathology ; Pancreatic Neoplasms/therapy ; Phosphatidylinositol 3-Kinases/metabolism ; Protein Transport/drug effects ; Protein Transport/genetics ; Protein Transport/radiation effects ; Proto-Oncogene Proteins c-akt/metabolism ; RNA, Small Interfering/genetics ; Radiation Tolerance/genetics ; Signal Transduction/drug effects ; Signal Transduction/radiation effects ; Treatment Failure
Chemical Substances	GTPase-Activating Proteins ; RNA, Small Interfering ; Ralbp1 protein, mouse ; Doxorubicin (80168379AG) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
Language	English
Publishing date	2012-04-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0034582
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Article ; Online: Targeting p53-null neuroblastomas through RLIP76.

Singhal, Jyotsana / Yadav, Sushma / Nagaprashantha, Lokesh Dalasanur / Vatsyayan, Rit / Singhal, Sharad S / Awasthi, Sanjay

Cancer prevention research (Philadelphia, Pa.)

2011 Volume 4, Issue 6, Page(s) 879–889

Abstract: The search for p53-independent mechanism of cancer cell killing is highly relevant to pediatric neuroblastomas, where successful therapy is limited by its transformation into p53-mutant and a highly drug-resistant neoplasm. Our studies on the drug- ... ...

Abstract	The search for p53-independent mechanism of cancer cell killing is highly relevant to pediatric neuroblastomas, where successful therapy is limited by its transformation into p53-mutant and a highly drug-resistant neoplasm. Our studies on the drug-resistant p53-mutant as compared with drug-resistant p53 wild-type neuroblastoma revealed a novel mechanism for resistance to apoptosis: a direct role of p53 in regulating the cellular concentration of proapoptotic alkenals by functioning as a specific and saturable allosteric inhibitor of the alkenal-glutathione conjugate transporter, RLIP76. The RLIP76-p53 complex was showed by both immunoprecipitation analyses of purified proteins and immunofluorescence analysis. Drug transport studies revealed that p53 inhibited both basal and PKCα-stimulated transport of glutathione conjugates of 4HNE (GSHNE) and doxorubicin. Drug resistance was significantly greater for p53-mutant as compared with p53 wild-type neuroblastoma cell lines, but both were susceptible to depletion of RLIP76 by antisense alone. In addition, inhibition of RLIP76 significantly enhanced the cytotoxicity of cisplatin. Taken together, these studies provide powerful evidence for a novel mechanism for drug and apoptosis resistance in p53-mutant neuroblastoma, based on a model of regulation of p53-induced apoptosis by RLIP76, where p53 is a saturable and specific allosteric inhibitor of RLIP76, and p53 loss results in overexpression of RLIP76; thus, in the absence of p53, the drug and glutathione-conjugate transport activities of RLIP76 are enhanced. Most importantly, our findings strongly indicate RLIP76 as a novel target for therapy of drug-resistant and p53-mutant neuroblastoma.
MeSH term(s)	ATP-Binding Cassette Transporters/antagonists & inhibitors ; ATP-Binding Cassette Transporters/genetics ; ATP-Binding Cassette Transporters/metabolism ; Animals ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Blotting, Western ; Child ; Cisplatin/administration & dosage ; Cross-Linking Reagents/pharmacology ; Doxorubicin/administration & dosage ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm/genetics ; GTPase-Activating Proteins/antagonists & inhibitors ; GTPase-Activating Proteins/genetics ; GTPase-Activating Proteins/metabolism ; Glutathione/metabolism ; Humans ; Immunoenzyme Techniques ; Immunoprecipitation ; Male ; Mice ; Mice, Nude ; Neuroblastoma/genetics ; Neuroblastoma/metabolism ; Neuroblastoma/prevention & control ; Oligonucleotides, Antisense/pharmacology ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53/physiology
Chemical Substances	ATP-Binding Cassette Transporters ; Cross-Linking Reagents ; GTPase-Activating Proteins ; Oligonucleotides, Antisense ; RALBP1 protein, human ; TP53 protein, human ; Tumor Suppressor Protein p53 ; Doxorubicin (80168379AG) ; Glutathione (GAN16C9B8O) ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2011-03-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2434717-6
ISSN	1940-6215 ; 1940-6207
ISSN (online)	1940-6215
ISSN	1940-6207
DOI	10.1158/1940-6207.CAPR-11-0025
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Article ; Online: Didymin induces apoptosis by inhibiting N-Myc and upregulating RKIP in neuroblastoma.

Singhal, Jyotsana / Nagaprashantha, Lokesh Dalasanur / Vatsyayan, Rit / Ashutosh / Awasthi, Sanjay / Singhal, Sharad S

Cancer prevention research (Philadelphia, Pa.)

2011 Volume 5, Issue 3, Page(s) 473–483

Abstract: Neuroblastomas arise from the neural crest cells and represent the most common solid tumors outside the nervous system in children. The amplification of N-Myc plays a primary role in the pathogenesis of neuroblastomas, whereas acquired mutations of p53 ... ...

Abstract	Neuroblastomas arise from the neural crest cells and represent the most common solid tumors outside the nervous system in children. The amplification of N-Myc plays a primary role in the pathogenesis of neuroblastomas, whereas acquired mutations of p53 lead to refractory and relapsed cases of neuroblastomas. In this regard, dietary compounds which can target N-Myc and exert anticancer effects independent of p53 status acquire significance in the management of neuroblastomas. Hence, we investigated the anticancer properties of the flavonoid didymin in neuroblastomas. Didymin effectively inhibited proliferation and induced apoptosis irrespective of p53 status in neuroblastomas. Didymin downregulated phosphoinositide 3-kinase, pAkt, Akt, vimentin, and upregulated RKIP levels. Didymin induced G(2)/M arrest along with decreasing the levels of cyclin D1, CDK4, and cyclin B1. Importantly, didymin inhibited N-Myc as confirmed at protein, mRNA, and transcriptional level by promoter-reporter assays. High-performance liquid chromatography analysis of didymin-treated (2 mg/kg b.w.) mice serum revealed effective oral absorption with free didymin concentration of 2.1 μmol/L. Further in vivo mice xenograft studies revealed that didymin-treated (2 mg/kg b.w.) animals had significant reductions in tumors size compared with controls. Didymin strongly inhibited the proliferation (Ki67) and angiogenesis (CD31) markers, as well as N-Myc expression, as revealed by the histopathologic examination of paraffin-embedded section of resected tumors. Collectively, our in vitro and in vivo studies elucidated the anticancer properties and mechanisms of action of a novel, orally active, and palatable flavonoid didymin, which makes it a potential new approach for neuroblastoma therapy (NANT) to target pediatric neuroblastomas.
MeSH term(s)	Animals ; Apoptosis/drug effects ; Blotting, Western ; Cell Cycle/drug effects ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Flavonoids/pharmacology ; Flow Cytometry ; Glycosides/pharmacology ; Humans ; Immunoenzyme Techniques ; Mice ; Mice, Nude ; Neuroblastoma/drug therapy ; Neuroblastoma/metabolism ; Neuroblastoma/pathology ; Phosphatidylethanolamine Binding Protein/antagonists & inhibitors ; Phosphatidylethanolamine Binding Protein/genetics ; Phosphatidylethanolamine Binding Protein/metabolism ; Proto-Oncogene Proteins c-myc/antagonists & inhibitors ; Proto-Oncogene Proteins c-myc/genetics ; Proto-Oncogene Proteins c-myc/metabolism ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Real-Time Polymerase Chain Reaction ; Tumor Cells, Cultured ; Up-Regulation
Chemical Substances	Flavonoids ; Glycosides ; PEBP1 protein, human ; Phosphatidylethanolamine Binding Protein ; Proto-Oncogene Proteins c-myc ; RNA, Messenger ; RNA, Small Interfering ; didymin
Language	English
Publishing date	2011-12-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2434717-6
ISSN	1940-6215 ; 1940-6207
ISSN (online)	1940-6215
ISSN	1940-6207
DOI	10.1158/1940-6207.CAPR-11-0318
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Article ; Online: Nutlin-3 enhances sorafenib efficacy in renal cell carcinoma.

Vatsyayan, Rit / Singhal, Jyotsana / Nagaprashantha, Lokesh Dalasanur / Awasthi, Sanjay / Singhal, Sharad S

Molecular carcinogenesis

2011 Volume 52, Issue 1, Page(s) 39–48

Abstract: The renal cell carcinoma (RCC) is one of the top 10 cancers in USA. The renal tumors are highly angiogenic and are resistant to conventional interventions, particularly radiotherapy. The advent of multi-specific tyrosine kinase inhibitor sorafenib has ... ...

Abstract	The renal cell carcinoma (RCC) is one of the top 10 cancers in USA. The renal tumors are highly angiogenic and are resistant to conventional interventions, particularly radiotherapy. The advent of multi-specific tyrosine kinase inhibitor sorafenib has improved the progression-free survival in RCC, but overall survival in recurrent and metastatic RCC is still a concern that has lead to characterization of combinatorial regimens. Hence, we studied the effect of combination of nutlin-3, an MDM2 inhibitor, which increases p53 levels, and sorafenib in RCC. Sorafenib along with nutlin-3 synergistically inhibited the cell survival and enhanced caspase-3 cleavage leading to apoptosis in RCC. Nutlin-3 and sorafenib were more effective in reducing the migration of RCC, in combination than as single agents. Sorafenib and nutlin-3 decreased the phosphorylation of vascular endothelial growth factor receptor-2 (VEGFR-2) and ERK along with inducing p53 activity. The sorafenib and nutlin-3 co-treatment lead to enhanced levels of p53, p-p53, and increase in the levels of p53 pro-apoptotic effector PUMA, Bax, and decrease in the anti-apoptotic Bcl-2 levels. Importantly, our studies revealed that sorafenib alone can activate p53 in a concentration dependent manner. Thus, co-treatment of nutlin-3 with sorafenib leads to increased half-life of p53, which in turn can be activated by sorafenib, to induce downstream pro-apoptotic and anti-proliferative effects. This is the first report showing the synergistic effect of sorafenib and nutlin-3 while providing a strong clinical-translational rationale for further testing of sorafenib and nutlin-3 combinatorial regimen in human RCC.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; Apoptosis/drug effects ; Apoptosis Regulatory Proteins/analysis ; Benzenesulfonates/pharmacology ; Carcinoma, Renal Cell/drug therapy ; Caspase 3/metabolism ; Cell Line, Tumor ; Cell Movement/drug effects ; Humans ; Imidazoles/pharmacology ; Kidney Neoplasms/drug therapy ; MAP Kinase Signaling System/drug effects ; Niacinamide/analogs & derivatives ; Phenylurea Compounds ; Phosphorylation ; Piperazines/pharmacology ; Proto-Oncogene Proteins/analysis ; Proto-Oncogene Proteins c-bcl-2/analysis ; Proto-Oncogene Proteins c-mdm2/antagonists & inhibitors ; Pyridines/pharmacology ; Sorafenib ; Tumor Suppressor Protein p53/analysis ; Vascular Endothelial Growth Factor Receptor-2/metabolism ; bcl-2-Associated X Protein/analysis
Chemical Substances	Antineoplastic Agents ; Apoptosis Regulatory Proteins ; BAX protein, human ; BBC3 protein, human ; Benzenesulfonates ; Imidazoles ; Phenylurea Compounds ; Piperazines ; Proto-Oncogene Proteins ; Proto-Oncogene Proteins c-bcl-2 ; Pyridines ; TP53 protein, human ; Tumor Suppressor Protein p53 ; bcl-2-Associated X Protein ; Niacinamide (25X51I8RD4) ; nutlin 3 (53IA0V845C) ; Sorafenib (9ZOQ3TZI87) ; MDM2 protein, human (EC 2.3.2.27) ; Proto-Oncogene Proteins c-mdm2 (EC 2.3.2.27) ; Vascular Endothelial Growth Factor Receptor-2 (EC 2.7.10.1) ; Caspase 3 (EC 3.4.22.-)
Language	English
Publishing date	2011-10-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1004029-8
ISSN	1098-2744 ; 0899-1987
ISSN (online)	1098-2744
ISSN	0899-1987
DOI	10.1002/mc.20875
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Article ; Online: The sensors and regulators of cell-matrix surveillance in anoikis resistance of tumors.

Nagaprashantha, Lokesh Dalasanur / Vatsyayan, Rit / Lelsani, Poorna Chandra Rao / Awasthi, Sanjay / Singhal, Sharad S

International journal of cancer

2010 Volume 128, Issue 4, Page(s) 743–752

Abstract: Normal cells continuously monitor the nature of their respective cellular microenvironment. They are equipped with an inherent molecular defense to detect changes that can precipitate and trigger an oncogenic cascade in the internal and external ... ...

Abstract	Normal cells continuously monitor the nature of their respective cellular microenvironment. They are equipped with an inherent molecular defense to detect changes that can precipitate and trigger an oncogenic cascade in the internal and external environment of cells. The process called anoikis unleashes many a characteristic molecular change in the cells which eventually program to cell death in response to cell detachment and inappropriate cellular attachment, both of which can otherwise potentiate the ability of cells to preferentially pursue a malignant course due to the release of molecular discipline which conforms them to a benign structural and functional spectrum. The initiation and propagation of signaling that serves as a switch to cell survival or cell death mediated by surveillance of cell microenvironment is comprised of many heterogeneous sets of molecules interacting mainly at the interface of cell-extracellular matrix. Transforming cells continuously reprogram their signaling characteristics in sensing and modulating the stimuli from cell surface molecules like integrins, cadherins and immunoglobulin family of cell adhesion molecules at adhesion complexes, which enables them to resist anoikis and metastasize to different organs. Actin cytoskeleton binds BIM and Bcl2 modifying factor (BMF), which are regulated by the adhesion status and consequent conformation of cytoskeleton in the cells. This review aims at an integrated synopsis of fundamental mechanisms of the critical interactions of cell surface molecules to facilitate a focused analysis of the differential regulation of signaling processes at cell-ECM junctions that collectively rein the anoikis resistance, which in turn impacts metastatic aggressiveness and drug resistance of tumors originating from respective organs.
MeSH term(s)	Animals ; Anoikis/physiology ; Cell-Matrix Junctions/metabolism ; Extracellular Matrix/metabolism ; Humans ; Neoplasms/metabolism ; Signal Transduction
Language	English
Publishing date	2010-12-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	218257-9
ISSN	1097-0215 ; 0020-7136
ISSN (online)	1097-0215
ISSN	0020-7136
DOI	10.1002/ijc.25725
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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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