uPAR and cathepsin B-mediated compartmentalization of JNK regulates the migration of glioma-initiating cells

Alapati, Kiranmai; Kesanakurti, Divya; Rao, Jasti S.; Dasari, Venkata Ramesh

doi:10.1016/j.scr.2014.02.008

Cited by 31 publications

(19 citation statements)

References 59 publications

(73 reference statements)

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“…Our current data on the changes in DUSP4 localization (together with increased ITGB1 signaling, which increases JNK phosphorylation (71, 73), in cells with a high GFAP‐δ/α ratio) can explain these observations. Interestingly, although pJNK localizes to the nucleus in most glioma cells (74), pJNK sequestration in the cytoplasm has been associated with increased glioma migration (75). Location‐specific pJNK alterations were beyond the scope of this research, but sequestration of signaling molecules by changes in the IF network of glioma cells has been previously reported (76–78) and might therefore be of interest for future studies.…”

Section: Discussionmentioning

confidence: 99%

GFAP alternative splicing regulates glioma cell–ECM interaction in a DUSP4‐dependent manner

Bodegraven¹,

Asperen²,

Sluijs³

et al. 2019

The FASEB Journal

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Gliomas are the most common primary brain tumors. Their highly invasive character and the heterogeneity of active oncogenic pathways within single tumors complicate the development of curative therapies and cause poor patient prognosis. Glioma cells express the intermediate filament protein glial fibrillary acidic protein (GFAP), and the level of its alternative splice variant GFAP‐δ, relative to its canonical splice variant GFAP‐α, is higher in grade IV compared with lower‐grade and lower malignant glioma. In this study we show that a high GFAP‐δ/α ratio induces the expression of the dual‐specificity phosphatase 4 (DUSP4) in focal adhesions. By focusing on pathways up‐ and downstream of DUSP4 that are involved in the cell‐extracellular matrix interaction, we show that a high GFAP‐δ/α ratio equips glioma cells to better invade the brain. This study supports the hypothesis that glioma cells with a high GFAP‐δ/α ratio are highly invasive and more malignant cells, thus making GFAP alternative splicing a potential therapeutic target.—Van Bodegraven, E. J., van Asperen, J. V., Sluijs, J. A., van Deursen, C. B. J., van Strien, M. E., Stassen, O. M. J. A., Robe, P. A. J., Hol, E. M. GFAP alternative splicing regulates glioma cell–ECM interaction in a DUSP4‐dependent manner. FASEB J. 33, 12941–12959 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 99%

GFAP alternative splicing regulates glioma cell–ECM interaction in a DUSP4‐dependent manner

Bodegraven¹,

Asperen²,

Sluijs³

et al. 2019

The FASEB Journal

View full text Add to dashboard Cite

show abstract

“…In glioma invasiveness, critical roles of the extracellular and membrane‐bound metalloproteinases (especially MMP‐2, MMP‐9, MMP‐14, MMP‐19, and ADAMTS) are well established (Eisele et al, ; Lettau et al, ; Overall & Lopez‐Otin ; Suzuki, Fujioka, Ikeda, Murayama, & Manome, ). The serine protease uPA (Persson et al, ) and the cysteine protease cathepsin‐B (Aggarwal & Sloane ; Alapati, Kesanakurti, Rao, & Dasari, ) are also of importance.…”

Section: Modulation Of Brain Extracellular Matrix By Proteases and Glmentioning

confidence: 99%

Glioma infiltration and extracellular matrix: key players and modulators

Ferrer

Moura‐Neto

Mentlein

2018

Glia

166

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An outstanding characteristic of gliomas is their infiltration into brain parenchyma, a property that impairs complete surgical resection; consequently, these tumors might recur, resulting in a high mortality rate. Gliomas invade along preferential routes, such as those along white matter tracts and in the perineuronal and perivascular spaces. Brain extracellular components and their partners and modulators play a crucial role in glioma cell invasion. This review presents an extensive survey of the literature, showing how the brain extracellular matrix (ECM) is modulated during the glioma infiltration process. We explore aspects of ECM interaction with glioma cells, reviewing the main glycosaminoglycans, glycoproteins and proteoglycans. We discuss the roles of ECM-binding proteins, including CD44, RHAMM, integrins and axonal guidance molecules, and highlight the role of proteases and glycosidases in glioma infiltration; in binding and release chemokines, cytokines and growth factors; and in generating new bioactive ECM fragments. We also consider the roles of cytoskeletal signaling, angiogenesis, miRNAs and the glial-to-mesenchymal transition linked to glioma invasion. We closely discuss therapeutic approaches based on the modulation of the extracellular matrix, targeting the control of glioma infiltration, its relative failure in clinical trials, and potential means to overcome this difficulty.

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“…The LYSTARs are remotely similar to the Ly6/uPAR superfamily. This superfamily includes secreted signaling proteins and receptors with diverse functions, including protection of cells from complementmediated lysis (Fletcher et al, 1994), modulation of neuronal excitability targeting nicotinic acetylcholine receptors (Lyukmanova et al, 2016;Tsetlin, 2015), cell adhesion and migration (Alapati et al, 2014;Hänninen et al, 1997), induction of chemotaxis of hematopoietic stem cells (Selleri et al, 2006), and antimicrobial activity (Liu et al, 2017). Because acetylcholine is the major excitatory neurotransmitter in echinoderms (Devlin, 2001) and affects mechanical properties of mutable collagenous tissue (Wilkie, 2002), it is tempting to assume that LYSTARs may act as endogenous modulators of acetylcholinergic transmission in starfish.…”

Section: Signal Transducersmentioning

confidence: 99%

Injury affects coelomic fluid proteome of the common starfishAsterias rubens

Shabelnikov

Bobkov

Sharlaimova

et al. 2019

Journal of Experimental Biology

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Echinoderms, possessing outstanding regenerative capabilities, provide a unique model system for the study of response to injury. However, little is known about the proteomic composition of coelomic fluid, an important biofluid circulating throughout the animal's body and reflecting the overall biological status of the organism. In this study, we used LC-MALDI tandem mass spectrometry to characterize the proteome of the cell-free coelomic fluid of the starfish Asterias rubens and to follow the changes occurring in response to puncture wound and blood loss. In total, 91 proteins were identified, of which 61 were extracellular soluble and 16 were bound to the plasma membrane. The most represented functional terms were 'pattern recognition receptor activity' and 'peptidase inhibitor activity'. A series of candidate proteins involved in early response to injury was revealed. Ependymin, β-microseminoprotein, serum amyloid A and avidin-like proteins, which are known to be involved in intestinal regeneration in the sea cucumber, were also identified as injuryresponsive proteins. Our results expand the list of proteins potentially involved in defense and regeneration in echinoderms and demonstrate dramatic effects of injury on the coelomic fluid proteome.

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uPAR and cathepsin B-mediated compartmentalization of JNK regulates the migration of glioma-initiating cells

Cited by 31 publications

References 59 publications

GFAP alternative splicing regulates glioma cell–ECM interaction in a DUSP4‐dependent manner

GFAP alternative splicing regulates glioma cell–ECM interaction in a DUSP4‐dependent manner

Glioma infiltration and extracellular matrix: key players and modulators

Injury affects coelomic fluid proteome of the common starfishAsterias rubens

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