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      The Role of Nonerythroid Spectrin αII in Cancer

      review-article
      ,
      Journal of Oncology
      Hindawi

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          Abstract

          Nonerythroid spectrin αII (SPTAN1) is an important cytoskeletal protein that ensures vital cellular properties including polarity and cell stabilization. In addition, it is involved in cell adhesion, cell-cell contact, and apoptosis. The detection of altered expression of SPTAN1 in tumors indicates that SPTAN1 might be involved in the development and progression of cancer. SPTAN1 has been described in cancer and therapy response and proposed as a potential marker protein for neoplasia, tumor aggressiveness, and therapeutic efficiency. On one hand, the existing data suggest that overexpression of SPTAN1 in tumor cells reflects neoplastic and tumor promoting activity. On the other hand, nuclear SPTAN1 can have tumor suppressing effects by enabling DNA repair through interaction with DNA repair proteins. Moreover, SPTAN1 cleavage products occur during apoptosis and could serve as markers for the efficacy of cancer therapy. Due to SPTAN1's multifaceted functions and its role in adhesion and migration, SPTAN1 can influence tumor growth and progression in both positive and negative directions depending on its specific regulation. This review summarizes the current knowledge on SPTAN1 in cancer and depicts several mechanisms by which SPTAN1 could impact tumor development and aggressiveness.

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          Most cited references114

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          Actin-based cell motility and cell locomotion.

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            FAK signaling in human cancer as a target for therapeutics.

            Focal adhesion kinase (FAK) is a key regulator of growth factor receptor- and integrin-mediated signals, governing fundamental processes in normal and cancer cells through its kinase activity and scaffolding function. Increased FAK expression and activity occurs in primary and metastatic cancers of many tissue origins, and is often associated with poor clinical outcome, highlighting FAK as a potential determinant of tumor development and metastasis. Indeed, data from cell culture and animal models of cancer provide strong lines of evidence that FAK promotes malignancy by regulating tumorigenic and metastatic potential through highly-coordinated signaling networks that orchestrate a diverse range of cellular processes, such as cell survival, proliferation, migration, invasion, epithelial-mesenchymal transition, angiogenesis and regulation of cancer stem cell activities. Such an integral role in governing malignant characteristics indicates that FAK represents a potential target for cancer therapeutics. While pharmacologic targeting of FAK scaffold function is still at an early stage of development, a number of small molecule-based FAK tyrosine kinase inhibitors are currently undergoing pre-clinical and clinical testing. In particular, PF-00562271, VS-4718 and VS-6063 show promising clinical activities in patients with selected solid cancers. Clinical testing of rationally designed FAK-targeting agents with implementation of predictive response biomarkers, such as merlin deficiency for VS-4718 in mesothelioma, may help improve clinical outcome for cancer patients. In this article, we have reviewed the current knowledge regarding FAK signaling in human cancer, and recent developments in the generation and clinical application of FAK-targeting pharmacologic agents.
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              Proteolysis of fodrin (non-erythroid spectrin) during apoptosis.

              Several recent studies have implicated proteases as important triggers of apoptosis. Thus far, substrates that are cleaved during apoptosis have been elusive. In this report we demonstrate that cleavage of alpha-fodrin (non-erythroid spectrin) accompanies apoptosis, induced by activation via the CD3/T cell receptor complex in a murine T cell hybridoma, ligation of the Fas (CD95) molecule on a human T cell lymphoma line and other Fas-expressing cells, or treatment of cells with staurosporine, dexamethasone, or synthetic ceramide. Furthermore, inhibition of activation-induced apoptosis by pretreatment of T hybridoma cells with antisense oligonucleotides directed against c-myc also inhibited fodrin proteolysis, confirming that this cleavage process is tightly coupled to apoptosis. Fodrin cleavage during apoptosis may have implications for the membrane blebbing seen during this process.
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                Author and article information

                Contributors
                Journal
                J Oncol
                J Oncol
                JO
                Journal of Oncology
                Hindawi
                1687-8450
                1687-8469
                2019
                2 May 2019
                : 2019
                : 7079604
                Affiliations
                Medical Clinic I, Biomedical Research Laboratory, University Clinic Frankfurt, Frankfurt am Main, Germany
                Author notes

                Academic Editor: Giandomenico Roviello

                Author information
                http://orcid.org/0000-0002-8320-5401
                http://orcid.org/0000-0003-1089-9710
                Article
                10.1155/2019/7079604
                6521328
                31186638
                9fe85c59-9cfc-480b-88df-598d566fdde1
                Copyright © 2019 Anne Ackermann and Angela Brieger.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 March 2019
                : 5 April 2019
                : 9 April 2019
                Funding
                Funded by: University Clinic Frankfurt
                Categories
                Review Article

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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