Synemin down-regulation in human hepatocellular carcinoma does not destabilize cytoskeletons in vivo

Liu, Yi-Hsiang; Cheng, Chiung-Chi; Lai, Yih-Shyong; Chao, Wei‐Ting; Pei, Ren-Jeng; Hsu, Yung-Hsiang; Ho, Ching-Chun

doi:10.1016/j.bbrc.2010.12.008

Cited by 6 publications

(5 citation statements)

References 25 publications

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“…In glioblastoma, synemin controls cell proliferation through AKT by antagonizing PP2A [36]. Interestingly, in human hepatocellular carcinomas, a down-regulation of synemin fails to alter the stability of the cytoskeleton, indicating the tissue specificity and multifunctionality of synemin [37]. In line with our findings of a synemin-DNA-PKcs interaction, synemin has been described as an IF protein with an inability to self-assemble into filaments [38].…”

Section: Discussionsupporting

confidence: 82%

The Intermediate Filament Synemin Regulates Non-Homologous End Joining in an ATM-Dependent Manner

Deville

Vehlow

Förster

et al. 2020

Cancers

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The treatment resistance of cancer cells is a multifaceted process in which DNA repair emerged as a potential therapeutic target. DNA repair is predominantly conducted by nuclear events; yet, how extra-nuclear cues impact the DNA damage response is largely unknown. Here, using a high-throughput RNAi-based screen in three-dimensionally-grown cell cultures of head and neck squamous cell carcinoma (HNSCC), we identified novel focal adhesion proteins controlling DNA repair, including the intermediate filament protein, synemin. We demonstrate that synemin critically regulates the DNA damage response by non-homologous end joining repair. Mechanistically, synemin forms a protein complex with DNA-PKcs through its C-terminal tail domain for determining DNA repair processes upstream of this enzyme in an ATM-dependent manner. Our study discovers a critical function of the intermediate filament protein, synemin in the DNA damage response, fundamentally supporting the concept of cytoarchitectural elements as co-regulators of nuclear events.

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Section: Discussionsupporting

confidence: 82%

The Intermediate Filament Synemin Regulates Non-Homologous End Joining in an ATM-Dependent Manner

Deville

Vehlow

Förster

et al. 2020

Cancers

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“…To investigate the time‐course effect of siPlectin on the phosphorylation of integrin α6β4, activation of FAK and p38, as well as induction of cell apoptosis, we collected podocyte at five different time‐points (24, 48, 72, 120 and 168 hours) after siPlectin was added to the podocyte culture medium. We chose these time‐points based on previous studies in which cells were collected 48 or 72 hours after siPlectin was added to the culture medium and significant down‐regulation of plectin expression and activation of downstream signalling pathways were demonstrated.…”

Section: Resultsmentioning

confidence: 99%

Plectin protects podocytes from adriamycin‐induced apoptosis and F‐actin cytoskeletal disruption through the integrin α6β4/FAK/p38 MAPK pathway

Wang

Yin³

et al. 2018

J Cellular Molecular Medi

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Podocyte injury is an early pathological change characteristic of various glomerular diseases, and apoptosis and F‐actin cytoskeletal disruption are typical features of podocyte injury. In this study, we found that adriamycin (ADR) treatment resulted in typical podocyte injury and repressed plectin expression. Restoring plectin expression protected against ADR‐induced podocyte injury whereas siRNA‐mediated plectin silencing produced similar effects as ADR‐induced podocyte injury, suggesting that plectin plays a key role in preventing podocyte injury. Further analysis showed that plectin repression induced significant integrin α6β4, focal adhesion kinase (FAK) and p38 MAPK phosphorylation. Mutating Y1494, a key tyrosine residue in the integrin β4 subunit, blocked FAK and p38 phosphorylation, thereby alleviating podocyte injury. Inhibitor studies demonstrated that FAK Y397 phosphorylation promoted p38 activation, resulting in podocyte apoptosis and F‐actin cytoskeletal disruption. In vivo studies showed that administration of ADR to rats resulted in significantly increased 24‐hour urine protein levels along with decreased plectin expression and activated integrin α6β4, FAK, and p38. Taken together, these findings indicated that plectin protects podocytes from ADR‐induced apoptosis and F‐actin cytoskeletal disruption by inhibiting integrin α6β4/FAK/p38 pathway activation and that plectin may be a therapeutic target for podocyte injury‐related glomerular diseases.

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“…The C-terminal domain of plakin mediates binding to intermediate filaments such as vimentin [ 32 ], while the plakin domain harbours interaction with integrin α6β4 [ 33 ] and BPAG2 (or type XV11 collagen) [ 11 ]. In muscle cells, PLEC can bind β-dystroglycan [ 34 ] and intermediate filament β-synemin [ 35 ], and the kinase Fer [ 36 ] in fibroblasts. The binding sites of these proteins are yet to be identified.…”

Section: Common Plakin Members: Their Structure and Function In Normal Cell Biologymentioning

confidence: 99%

“…Induced PLEC deficiency in healthy hepatocytes also showed augmented cytoskeletons, through the altered expression and rearrangement of cytokeratin 18 (CK18). PLEC’s role in the spatial organisation and anchorage of the cytoskeleton is phosphorylation-dependent, as PLEC’s coordination of lamin B and vimentin is modulated by protein kinase A and protein kinase C [ 35 ]. In addition, the breast cancer susceptibility protein, BRCA2, interacts with PLEC [ 89 ], where the BRCA2/PLEC complex is involved in nuclear duplication and centrosome formation.…”

Section: Plakins In Cancermentioning

confidence: 99%

The attributes of plakins in cancer and disease: perspectives on ovarian cancer progression, chemoresistance and recurrence

et al. 2021

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The plakin family of cytoskeletal proteins play an important role in cancer progression yet are under-studied in cancer, especially ovarian cancer. These large cytoskeletal proteins have primary roles in the maintenance of cytoskeletal integrity but are also associated with scaffolds of intermediate filaments and hemidesmosomal adhesion complexes mediating signalling pathways that regulate cellular growth, migration, invasion and differentiation as well as stress response. Abnormalities of plakins, and the closely related spectraplakins, result in diseases of the skin, striated muscle and nervous tissue. Their prevalence in epithelial cells suggests that plakins may play a role in epithelial ovarian cancer progression and recurrence. In this review article, we explore the roles of plakins, particularly plectin, periplakin and envoplakin in disease-states and cancers with emphasis on ovarian cancer. We discuss the potential role the plakin family of proteins play in regulating cancer cell growth, survival, migration, invasion and drug resistance. We highlight potential relationships between plakins, epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) and discuss how interaction of these processes may affect ovarian cancer progression, chemoresistance and ultimately recurrence. We propose that molecular changes in the expression of plakins leads to the transition of benign ovarian tumours to carcinomas, as well as floating cellular aggregates (commonly known as spheroids) in the ascites microenvironment, which may contribute to the sustenance and progression of the disease. In this review, attempts have been made to understand the crucial changes in plakin expression in relation to progression and recurrence of ovarian cancer.

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Synemin down-regulation in human hepatocellular carcinoma does not destabilize cytoskeletons in vivo

Cited by 6 publications

References 25 publications

The Intermediate Filament Synemin Regulates Non-Homologous End Joining in an ATM-Dependent Manner

The Intermediate Filament Synemin Regulates Non-Homologous End Joining in an ATM-Dependent Manner

Plectin protects podocytes from adriamycin‐induced apoptosis and F‐actin cytoskeletal disruption through the integrin α6β4/FAK/p38 MAPK pathway

The attributes of plakins in cancer and disease: perspectives on ovarian cancer progression, chemoresistance and recurrence

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