Role of cytoskeletal proteins in cerebral cavernous malformation signaling pathways: a proteomic analysis

Baxter, Sarah Schwartz; Dibble, Christopher F.; Byrd, Warren C.; Carlson, James E.; Mack, C. Russell; Saldarriaga, Ivandario; Bencharit, Sompop

doi:10.1039/c3mb70199a

Cited by 12 publications

(7 citation statements)

References 43 publications

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“…However, p53 expression remained largely unaltered in TRIM59 KD MCF7 cells, thus clearly indicating the existence of a p53-independent mechanism. Notably, proteomic mapping of PDCD10 interactors has identified proteins involved in the regulation of G0/G1-S phase transition of the cell cycle, such as cytoskeletal protein guanine nucleotide-binding protein subunit beta-like protein (GBLP) [ 14 , 64 ]. Further analysis is needed to clarify whether PDCD10 is directly responsible for the function of TRIM59 in cell survival and cell cycle regulation.…”

Section: Discussionmentioning

confidence: 99%

TRIM59 promotes breast cancer motility by suppressing p62-selective autophagic degradation of PDCD10

Tan

et al. 2018

PLoS Biol

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Cancer cells adopt various modes of migration during metastasis. How the ubiquitination machinery contributes to cancer cell motility remains underexplored. Here, we report that tripartite motif (TRIM) 59 is frequently up-regulated in metastatic breast cancer, which is correlated with advanced clinical stages and reduced survival among breast cancer patients. TRIM59 knockdown (KD) promoted apoptosis and inhibited tumor growth, while TRIM59 overexpression led to the opposite effects. Importantly, we uncovered TRIM59 as a key regulator of cell contractility and adhesion to control the plasticity of metastatic tumor cells. At the molecular level, we identified programmed cell death protein 10 (PDCD10) as a target of TRIM59. TRIM59 stabilized PDCD10 by suppressing RING finger and transmembrane domain-containing protein 1 (RNFT1)-induced lysine 63 (K63) ubiquitination and subsequent phosphotyrosine-independent ligand for the Lck SH2 domain of 62 kDa (p62)-selective autophagic degradation. TRIM59 promoted PDCD10-mediated suppression of Ras homolog family member A (RhoA)-Rho-associated coiled-coil kinase (ROCK) 1 signaling to control the transition between amoeboid and mesenchymal invasiveness. PDCD10 overexpression or administration of a ROCK inhibitor reversed TRIM59 loss-induced contractile phenotypes, thereby accelerating cell migration, invasion, and tumor formation. These findings establish the rationale for targeting deregulated TRIM59/PDCD10 to treat breast cancer.

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Section: Discussionmentioning

confidence: 99%

TRIM59 promotes breast cancer motility by suppressing p62-selective autophagic degradation of PDCD10

Tan

et al. 2018

PLoS Biol

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“…TCPB, which serves as a molecular chaperon by assisting the folding of proteins upon the adenosine triphosphate (ATP) hydrolysis, is known to play a role in actin and tubulin formation in vitro [ 70 ]. Although this study presented TCPB down-regulation in high doxorubicin-resistant FISS, there is only one other study presenting its down-regulation in TS1-resistant pancreatic cancer cells, which indicates their role in chemosensitivity for TS1—a novel oral anticancer agent containing two biochemical modulators for 5-fluorouracil (5-FU) and tegafur, a metabolically activated prodrug of 5-FU [ 71 ].…”

Section: Discussionmentioning

confidence: 99%

Proteomic Differences in Feline Fibrosarcomas Grown Using Doxorubicin-Sensitive and -Resistant Cell Lines in the Chick Embryo Model

Zabielska-Koczywąs

Michalak

Wojtalewicz

et al. 2018

IJMS

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Proteomic analyses are rapid and powerful tools that are used to increase the understanding of cancer pathogenesis, discover cancer biomarkers and predictive markers, and select and monitor novel targets for cancer therapy. Feline injection-site sarcomas (FISS) are aggressive skin tumours with high recurrence rates, despite treatment with surgery, radiotherapy, and chemotherapy. Doxorubicin is a drug of choice for soft tissue sarcomas, including FISS. However, multidrug resistance is one of the major causes of chemotherapy failure. The main aim of the present study was to identify proteins that differentiate doxorubicin-resistant from doxorubicin-sensitive FISS using two-dimensional gel electrophoresis (2DE), followed by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) analysis. Using the three-dimensional (3D) preclinical in ovo model, which resembles features of spontaneous fibrosarcomas, three significantly (p ≤ 0.05) differentially expressed proteins were identified in tumours grown from doxorubicin-resistant fibrosarcoma cell lines (FFS1 and FFS3) in comparison to the doxorubicin-sensitive one (FFS5): Annexin A5 (ANXA5), Annexin A3 (ANXA3), and meiosis-specific nuclear structural protein 1 (MNS1). Moreover, nine other proteins were significantly differentially expressed in tumours grown from the high doxorubicin-resistant cell line (FFS1) in comparison to sensitive one (FFS5). This study may be the first proteomic fingerprinting of FISS reported, identifying potential candidates for specific predictive biomarkers and research targets for doxorubicin-resistant FISS.

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“…CCM proteins directly interact with each another to form a CCM1-CCM2-CCM3 based signaling platform (68 , 69) with interacting proteins rather distinct for each CCM protein (19 - 21 , 70 - 72) . Interaction between CCM2 and CCM3 is necessary for stability of the two proteins (73) and CCM2 dependent stabilization of CCM1 has also been reported (49) .…”

Section: Formation Of a Heterotrimeric Ccm1-ccm2-ccm3 ‘Ccm Complex Simentioning

confidence: 99%

“…1 ). Indeed, both in vivo and in vitro studies revealed that perturbation of the WNT/β-catenin pathway (10 , 11) , TGF-β/BMP (10 , 12 , 13) and Notch signaling (14) , cytoskeletal regulation (8 , 15) and anti-oxidant signaling (16 - 18) are responsible for CCM pathogenesis and several proteomic studies elegantly showed that all three ccm genes encode CCM proteins comprising distinct macromolecular complexes, implying complex regulation of multiple signaling pathways due to various interactions with many signaling molecules by each CCM protein (19 - 21) . As individual proteins comprising the distinct macromolecular CCM complexes are still not fully characterized, our understanding of the composition of the CCM macromolecular complexes and associated functional networks is still in its infancy.…”

Section: Introductionmentioning

confidence: 99%

Introduction to cerebral cavernous malformation: a brief review

Kim

2016

BMB Reports

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The disease known as cerebral cavernous malformations mostly occurs in the central nervous system, and their typical histological presentations are multiple lumen formation and vascular leakage at the brain capillary level, resulting in disruption of the blood-brain barrier. These abnormalities result in severe neurological symptoms such as seizures, focal neurological deficits and hemorrhagic strokes. CCM research has identified ‘loss of function’ mutations of three ccm genes responsible for the disease and also complex regulation of multiple signaling pathways including the WNT/β-catenin pathway, TGF-β and Notch signaling by the ccm genes. Although CCM research is a relatively new and small scientific field, as CCM research has the potential to regulate systemic blood vessel permeability and angiogenesis including that of the blood-brain barrier, this field is growing rapidly. In this review, I will provide a brief overview of CCM pathogenesis and function of ccm genes based on recent progress in CCM research. [BMB Reports 2016; 49(5): 255-262]

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Role of cytoskeletal proteins in cerebral cavernous malformation signaling pathways: a proteomic analysis

Abstract: An in vitro proteomics and systems biology of cerebral cavernous malformation.

Cited by 12 publications

References 43 publications

TRIM59 promotes breast cancer motility by suppressing p62-selective autophagic degradation of PDCD10

TRIM59 promotes breast cancer motility by suppressing p62-selective autophagic degradation of PDCD10

Proteomic Differences in Feline Fibrosarcomas Grown Using Doxorubicin-Sensitive and -Resistant Cell Lines in the Chick Embryo Model

Introduction to cerebral cavernous malformation: a brief review

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