Department Of Biochemistry And Microbial Sciences

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Author: search.filters.author.Baranwal, SomeshHas files: Yes

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    Exosomes from Nischarin-Expressing Cells Reduce Breast Cancer Cell Motility and tumor growth.
    (Americal Association for Cancer Research, 2019) Maziveyi, M; Dong, S; Baranwal, Somesh; Mehrnezhad, A; Ratthinam, R; Huckaba, TM; Mercante, DE; Park, K; Alahari, SK
    Exosomes are small extracellular microvesicles that are secreted by cells when intracellular multivesicular bodies (MVB) fuse with the plasma membrane. We have previously demonstrated that Nischarin inhibits focal adhesion formation, cell migration, and invasion, leading to reduced activation focal adhesion kinase. In this study, we propose that the tumor suppressor Nischarin regulates the release of exosomes. When co-cultured on exosomes from Nischarin-positive cells, breast cancer cells exhibited reduced survival, migration, adhesion, and spreading. The same co-cultures formed xenograft tumors of significantly reduced volume following injection into mice. Exosomes secreted by Nischarin-expressing tumors inhibited tumor growth. Expression of only one allele of Nischarin increased secretion of exosomes, and Rab14 activity modulated exosome secretions and cell growth. Taken together, the present study reveals a novel role for Nischarin in preventing cancer cell motility, which contributes to our understanding of exosome biology.
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    Nischarin regulates focal adhesion and Invadopodia formation in breast cancer cells
    (BioMed Central Ltd., 2018) Mazvita Maziveyi; Dong, Shengli; Baranwal, Somesh; Alahari, Suresh K.; Maziveyi, M.; Dong, S.; Baranwal, S.; Alahari, S.K.
    Background: During metastasis, tumor cells move through the tracks of extracellular matrix (ECM). Focal adhesions (FAs) are the protein complexes that link the cell cytoskeleton to the ECM and their presence is necessary for cell attachment. The tumor suppressor Nischarin interacts with a number of signaling proteins such as Integrin ?5, PAK1, LIMK1, LKB1, and Rac1 to prevent cancer cell migration. Although previous findings have shown that Nischarin exerts this migratory inhibition by interacting with other proteins, the effects of these interactions on the entire FA machinery are unknown. Methods: RT-PCR, Western Blotting, invadopodia assays, and immunofluorescence were used to examine FA gene expression and determine whether Nischarin affects cell attachment, as well as the proteins that regulate it. Results: Our data show that Nischarin prevents cell migration and invasion by altering the expression of key focal adhesion proteins. Furthermore, we have found that Nischarin-expressing cells have reduced ability to attach the ECM, which in turn leads to a decrease in invadopodia-mediated matrix degradation. Conclusions: These experiments demonstrate an important role of Nischarin in regulating cell attachment, which adds to our understanding of the early events of the metastatic process in breast cancer. ? 2018 The Author(s).
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    Nischarin inhibition alters energy metabolism by activating AMP-activated protein kinase
    (American Society for Biochemistry and Molecular Biology Inc., 2017) Dong, Shengli; Baranwal, Somesh; Garcia, Anapatricia; Serrano-Gomez, Silvia; Eastlack, Steven; Iwakuma, Tomoo; Mercante, Donald; Mauvais-Jarvis, Franck; Alahari, Suresh K.; Dong, S.; Baranwal, S.; Garcia, A.; Serrano-Gomez, S.J.; Eastlack, S.; Iwakuma, T.; Mercante, D.; Mauvais-Jarvis, F.; Alahari, S.K.
    Nischarin (Nisch) is a key protein functioning as a molecular scaffold and thereby hosting interactions with several protein partners. To explore the physiological importance of Nisch, here we generated Nisch loss-of-function mutant mice and analyzed their metabolic phenotype. Nisch-mutant embryos exhibited delayed development, characterized by small size and attenuated weight gain. We uncovered the reason for this phenotype by showing that Nisch binds to and inhibits the activity of AMP-activated protein kinase (AMPK), which regulates energy homeostasis by suppressing anabolic and activating catabolic processes. The Nisch mutations enhanced AMPK activation and inhibited mechanistic target of rapamycin signaling in mouse embryonic fibroblasts as well as in muscle and liver tissues of mutant mice. Nisch-mutant mice also exhibited increased rates of glucose oxidation with increased energy expenditure, despite reduced overall food intake. Moreover, the Nisch-mutant mice had reduced expression of liver markers of gluconeogenesis associated with increased glucose tolerance. As a result, these mice displayed decreased growth and body weight. Taken together, our results indicate that Nisch is an important AMPK inhibitor and a critical regulator of energy homeostasis, including lipid and glucose metabolism. ? 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
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    Book Review: Gastrointestinal Physiology and Diseases Methods and Protocols
    (Frontiers in Cellular and Infection Microbiology, 2017) Baranwal, Somesh
    The gastrointestinal tract is one of the largest immunological organs and plays a pivotal role in maintaining normal homeostasis in the body. The statement made by Hippocrates more than 2,000 years ago “all disease begins in the gut” still holds true today. Studies in the past decades have revealed the importance of the gastrointestinal tract to human health. Defects in the digestive tract contribute to hundreds of medical conditions. Building upon the format of the Methods in Molecular Biology series, this book presents 29 protocols (divided into five parts) that mainly focus on the recent development of animal models to study gastrointestinal inflammation and disease progression.