Stress-activated Protein Kinase Pathways and Metastasis PDF Download

Author: Donald James Vander Griend
Publisher:
ISBN:
Category : Cancer
Languages : en
Pages : 322

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Author: Francesc Posas
Publisher: Springer Science & Business Media
ISBN: 3540755691
Category : Science
Languages : en
Pages : 322

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In this book leading researchers in the field discuss the state-of-the-art of many aspects of SAPK signaling in various systems from yeast to mammals. These include various chapters on regulatory mechanisms as well as the contribution of the SAPK signaling pathways to processes such as gene expression, metabolism, cell cycle regulation, immune responses and tumorigenesis. Written by international experts, the book will appeal to cell biologists and biochemists.

Author: Tzu-Hao Wang
Publisher:
ISBN:
Category :
Languages : en
Pages : 426

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Author: Qian-yu Guo
Publisher:
ISBN:
Category :
Languages : en
Pages :

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"Cancer metastasis is a multi-step process. This thesis focuses on two critical steps of the metastatic process in breast cancer: (1) the transition from non-invasive to invasive disease, and (2) immune evasion that supports metastasis. MAP kinase-interacting serine/threonine-protein kinases 1 and 2 (MNK1/2) are ubiquitously expressed serine/threonine kinases downstream of the ERK1/2 and p38 pathways. Hyper-activation of MNK1/2 due to external stimuli such as growth factors or stress signaling can enhance tumor cell invasion and metastasis in multiple solid malignancies including breast cancer, but the molecular mechanisms underpinning these effects of MNK1/2 remain largely unknown. Using in vitro and in vivo models, we demonstrated a novel function of MNK1, where the kinase drives the transition of breast ductal carcinoma in situ (DCIS), a non-invasive “stage 0” disease, into invasive ductal carcinoma (IDC). At the mechanistic level, MNK1 upregulates the expression of NODAL, a pro-tumorigenic morphogen, to support a partial epithelial-mesenchymal transition (EMT), and to maintain cancer stemness properties that increase the risk of tumor relapse and metastasis. The best characterized function of MNK1/2 is to phosphorylate the eukaryotic translation initiation factor 4E (eIF4E) at Ser209. Multiple pro-oncogenic pathways converge on the MNK1/2-eIF4E axis, which serves as a critical regulator of the translation of mRNAs that encode for proteins that promote cell invasion. The MNK1/2-eIF4E axis has been recently reported to reinforce the survival of pro-metastatic neutrophils in breast cancer. However, our knowledge of how aberrant mRNA translation regulates breast tumor immunity remains limited. We chose to study post-partum breast cancer (PPBC), an aggressive subtype of breast cancer, as it has been characterized by robust immune cell suppression, to examine how the MNK1/2-eIF4E axis shapes pro-tumorigenic immunity during metastasis. We demonstrate that eIF4E phosphorylation is important to support tumor immune evasion for PPBC metastasis. Using a mouse model that is devoid of eIF4E phosphorylation, and inhibitors of MNK1/2, we show that type 2 innate lymphoid cell (ILC2) function, myeloid-derived suppressor cells (MDSCs) accumulation, and cytotoxic T cell exclusion, are dependent on the MNK1/2-eIF4E axis. Immune targeted therapies have not shown great promise in breast cancer. We showed that the inhibition of MNK1/2 using the inhibitor SEL201, can work in concert with anti-PD1 immune targeted therapy to inhibit PPBC metastasis. Thus, we show the possibility of enhancing the efficacy of immunotherapy by using a small molecule inhibitor that blocks mRNA translation"--

Author: Paula Espino
Publisher:
ISBN:
Category :
Languages : en
Pages : 420

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Cell signaling -- MSK1 -- H3 phosphorylation -- chromatin -- cancer -- gene expression.

Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 10

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Mitogen activated protein kinase kinase 4 (MKK4) a member of the stress activated protein kinase signaling pathway acts as a metastasis suppressor protein in ovarian cancer. Introduction of MKK4 into a highly metastatic human ovarian cancer cell line reduces the number of overt metastases by 90% and prolongs animal survival by 70%. Our specific aims in this proposal included determining the mechanism by which MKK4 mediated metastasis suppression and determining whether introduction of MKK4 a potent activator of the JNK pathway in conjunction with chemotherapeutic agents known to activate JNK would potentiate MKK4s effects on survival and JNK activation. Our key findings during the period of the proposal included the following: 1) MKK4 mediates metastasis suppression via the p38 pathway 2) MKK4 does not mediate metastasis suppression via the JNK pathway 3) MKK4 kinase activity is required for MKK4 induced metastasis suppression. In the past year our findings have included 4) MKK4 expression does not augment the effects of either cisplatin or paclitaxel on metastases in vivo. 5) There do not appear to be any differences in JNK or p38 activation levels in metastases taken from mice injected with MKK4 and treated with chemotherapy (cisplatin or paclitaxel) over chemotherapy alone.

Author: Derek LeRoith
Publisher: Lippincott Williams & Wilkins
ISBN: 9780781740975
Category : Medical
Languages : es
Pages : 1606

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Thoroughly revised and updated, this Third Edition encompasses the most recent advances in molecular and cellular research and describes the newest therapeutic modalities for type 1 and type 2 diabetes mellitus. Chapters by leading experts integrate the latest basic science and clinical research on diabetes mellitus and its complications. The text is divided into ten major sections, including extensive sections on therapeutics, diabetes during pregnancy, and complications. New chapters cover stem cell therapy for type 1 diabetes; genetics and treatment of obesity; new therapies to promote insulin action; vasculopathy; islet cell protocols; triglycerides in muscle; hypoglycemia in the adult; and the Diabetes Prevention Program.

Author: David A. Frank
Publisher: Springer Science & Business Media
ISBN: 1402073402
Category : Medical
Languages : en
Pages : 358

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One of the most exciting areas of cancer research now is the development of agents which can target signal transduction pathways that are activated inappropriately in malignant cells. The understanding of the molecular abnormalities which distinguish malignant cells from their normal counterparts has grown tremendously. This volume summarizes the current research on the role that signal transduction pathways play in the pathogenesis of cancer and how this knowledge may be used to develop the next generation of more effective and less toxic anticancer agents. Series Editor comments: "The biologic behavior of both normal and cancer cells is determined by critical signal transduction pathways. This text provides a comprehensive review of the field. Leading investigators discuss key molecules that may prove to be important diagnostic and/or therapeutic targets."

Author: Deborah Marie Brancho
Publisher:
ISBN:
Category :
Languages : en
Pages : 396

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Author: Robert Clarke
Publisher: Springer
ISBN: 303005067X
Category : Medical
Languages : en
Pages : 220

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Book Description
This volume presents state-of-the-art information on each of the arms of the unfolded protein response (UPR), how their activation/repression are regulated, integrated, and coordinated, how UPR components affect cancer cell biology and responsiveness to therapeutic interventions, and how UPR components/activities offer potentially novel targets for drug discovery, repurposing, and development. The volume will provide the most recent information on the signaling and regulation of the UPR, explore examples of how the UPR and/or specific components contribute to cancer biology, and identify and explore specific examples of potently new actionable targets for drug discovery and development from within the UPR and its regulation. Unique to the volume will be a specific focus on the UPR and its role in cancer biology, as well as a discussion of the role of the UPR in drug responses and resistance in cancer.