Nesprin-1 impact on tumorigenic cell phenotypes

Sur-Erdem, İlknur; Hussain, Muhammad Sajid; Asif, Maria; Pınarbası, Nareg; Aksu, Ali Cenk; Noegel, Angelika A.

doi:10.1007/s11033-019-05184-w

Cited by 16 publications

(13 citation statements)

References 64 publications

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“…However, we found that the LINC complex is not required for the perinuclear actin formation in B16–F10 cells ( Figure 4 ) and it does not support migration of these cells ( Figure 5 ). Our results are in agreement with previous findings showing that the LINC complex is dispensable for NIH3T3 perinuclear actin rim formation [ 43 ] and that components of the LINC complex are down-regulated in cancer [ 50 , 51 , 52 , 53 , 54 , 55 ]. Thus, we estimate that an additional mechanism to the LINC complex links the nuclear envelope to the cytoplasmic actin cytoskeleton, a mechanism that is sensitive to high levels of lamin B1.…”

Section: Discussionsupporting

confidence: 94%

Increased Lamin B1 Levels Promote Cell Migration by Altering Perinuclear Actin Organization

Fracchia

Asraf

Salmon‐Divon

et al. 2020

Cells

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Cell migration requires reposition and reshaping of the cell nucleus. The nuclear lamina is highly important for migration of both primary and cancer cells. B-type lamins are important for proper migration of epicardial cells and neurons and increased lamin B to lamin A ratio accelerates cancer cell migration through confined spaces. Moreover, a positive association between lamin B1 levels and tumor formation and progression is found in various cancer types. Still, the molecular mechanism by which B-type lamins promote cell migration is not fully understood. To better understand this mechanism, we tested the effects of lamin B1 on perinuclear actin organization. Here we show that induction of melanoma cell migration leads to the formation of a cytosolic Linker of Nucleoskeleton and Cytoskeleton (LINC) complex-independent perinuclear actin rim, which has not been detected in migrating cells, yet. Significantly, increasing the levels of lamin B1 but not the levels of lamin A prevented perinuclear actin rim formation while accelerated the cellular migration rate. To interfere with the perinuclear actin rim, we generated a chimeric protein that is localized to the outer nuclear membrane and cleaves perinuclear actin filaments in a specific manner without disrupting other cytosolic actin filaments. Using this tool, we found that disruption of the perinuclear actin rim accelerated the cellular migration rate in a similar manner to lamin B1 over-expression. Taken together, our results suggest that increased lamin B1 levels can accelerate cell migration by inhibiting the association of the nuclear envelope with actin filaments that may reduce nuclear movement and deformability.

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Section: Discussionsupporting

confidence: 94%

Increased Lamin B1 Levels Promote Cell Migration by Altering Perinuclear Actin Organization

Fracchia

Asraf

Salmon‐Divon

et al. 2020

Cells

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“…Impairment in the expression level or full functionality of the LINC complex leads to development or disease progression in numerous types of cancers [ 35 ]. Dysregulation, dysfunction, or mutation in SYNE1/Nesprin-1 plays an important role in oral cancer [ 36 ], glioblastoma [ 24 ], breast cancer [ 37 ], ovarian cancer [ 19 ] and HCC [ 38 , 39 ], possibly through the regulation of cell proliferation and apoptosis [ 40 ]. A report published by Shaglof et al had demonstrated that one rarely studied isoform derived from alternatively spliced variants of SYNE1/Nesprin-1, named X6, was elevated in HCC-bearing rats, which might play a role in hepatocarcinogenesis and cancer progression [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…This may be caused by reduced LINC complex function due to repressed SYNE1 expression. Recent studies have shown that alterations in the nuclear envelope and LINC complex function might directly contribute to tumorigenesis, as disrupted nuclear envelope structures render the cells more prone to dysregulated mitosis [ 24 , 35 , 36 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

SYNE1 Exonic Variant rs9479297 Contributes to Concurrent Hepatocellular and Transitional Cell Carcinoma Double Primary Cancer

et al. 2021

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Unexpected high risk of synchronous/metachronous hepatocellular carcinoma (HCC) and transitional cell carcinoma (TCC) co-occurrence has been discovered previously. Here, we searched for genetic variation contributing to the co-occurrence of this double primary cancer (DPC). Using targeted exome sequencing, a panel of variants associated with concurrent DPC was identified. However, only a nonsynonymous variant within the Spectrin Repeat Containing Nuclear Envelope Protein 1 (SYNE1) gene was associated with DPC occurrence (p = 0.002), compared with that in the healthy population. Further independent cohort verification analysis revealed that the SYNE1-rs9479297-TT genotype (versus TC + CC genotypes) was enriched in patients with DPC, compared with that in those with TCC alone (p = 0.039), those with HCC alone (p = 0.006), those with non-HCC/non-TCC (p < 0.001), and healthy population (p < 0.001). SYNE1 mRNA expression reduced in both patients with HCC and TCC, and its lower expression in HCC was associated with shorter recurrence-free (p = 0.0314) and metastasis-free (p = 0.0479) survival. SYNE1-rs9479297 genotypes were correlated with tissue SYNE1 levels and clinical outcomes in HCC patients. Finally, SYNE1 silencing enhanced the cell proliferation and migration of HCC/TCC cells. In conclusion, SYNE1-rs9479297 genotypes were associated with HCC/TCC DPC co-occurrence and correlated with SYNE1 expression, which in turn contributed to HCC/TCC cell proliferation and migration, thereby affecting clinical outcomes.

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“…Among them, nesprin-1, -2, -3 and -4 are distinguished [ 76 ]. Numerous reports indicate that nesprin-1 is downregulated in oncological diseases, while mutations in SYNE1 have been identified in different types of human cancers [ 77 , 78 , 79 , 80 ]. In turn, induced overexpression of nesprin-1 allows reversing the malignant phenotype of human liver cancer Huh7 cell line [ 77 ].…”

Section: Actin and Abps In Carcinogenesismentioning

confidence: 99%

Involvement of Actin and Actin-Binding Proteins in Carcinogenesis

Izdebska

Zielińska

Hałas‐Wiśniewska

et al. 2020

Cells

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The actin cytoskeleton plays a crucial role in many cellular processes while its reorganization is important in maintaining cell homeostasis. However, in the case of cancer cells, actin and ABPs (actin-binding proteins) are involved in all stages of carcinogenesis. Literature has reported that ABPs such as SATB1 (special AT-rich binding protein 1), WASP (Wiskott-Aldrich syndrome protein), nesprin, and villin take part in the initial step of carcinogenesis by regulating oncogene expression. Additionally, changes in actin localization promote cell proliferation by inhibiting apoptosis (SATB1). In turn, migration and invasion of cancer cells are based on the formation of actin-rich protrusions (Arp2/3 complex, filamin A, fascin, α-actinin, and cofilin). Importantly, more and more scientists suggest that microfilaments together with the associated proteins mediate tumor vascularization. Hence, the presented article aims to summarize literature reports in the context of the potential role of actin and ABPs in all steps of carcinogenesis.

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Nesprin-1 impact on tumorigenic cell phenotypes

Cited by 16 publications

References 64 publications

Increased Lamin B1 Levels Promote Cell Migration by Altering Perinuclear Actin Organization

Increased Lamin B1 Levels Promote Cell Migration by Altering Perinuclear Actin Organization

SYNE1 Exonic Variant rs9479297 Contributes to Concurrent Hepatocellular and Transitional Cell Carcinoma Double Primary Cancer

Involvement of Actin and Actin-Binding Proteins in Carcinogenesis

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