The Acetylenic Tricyclic Bis(cyano enone), TBE-31 Inhibits Non–Small Cell Lung Cancer Cell Migration through Direct Binding with Actin

Chan, Edward; Saito, Akira; Honda, Tadashi; Guglielmo, Gianni M. Di

doi:10.1158/1940-6207.capr-13-0403

Cited by 15 publications

(16 citation statements)

References 48 publications

(92 reference statements)

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“…Actin filaments are an important component of the cytoskeleton that play a critical role in maintaining cell structure and regulating cell movement [16]. CAPZA1 is an actin-binding protein that is intimately involved in actin filament assembly [17].…”

Section: Resultsmentioning

confidence: 99%

CAPZA1 modulates EMT by regulating actin cytoskeleton remodelling in hepatocellular carcinoma

Deng

Cao

Zheng

2017

J Exp Clin Cancer Res

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BackgroundEpithelial-mesenchymal transition (EMT) elicits dramatic changes, including cytoskeleton remodelling as well as changes in gene expression and cellular phenotypes. During this process, actin filament assembly plays an important role in maintaining the morphology and movement of tumour cells. Capping protein, a protein complex referred to as CapZ, is an actin-binding complex that can regulate actin cytoskeleton remodelling. CAPZA1 is the α1 subunit of this complex, and we hypothesized that CAPZA1 regulates EMT through the regulation of actin filaments assembly, thus reducing the metastatic ability of hepatocellular carcinoma (HCC) cells.MethodsImmunohistochemistry was used to detect CAPZA1 expression in 129 HCC tissues. Western blotting and qPCR were used to detect CAPZA1, EMT markers and EMT transcription factors in HCC cells. Transwell migration and invasion assays were performed to observe the migration and invasion of HCC cells. Cell Counting Kit-8 (CCK-8) was used to detect the proliferation of HCC cells. Immunoprecipitation was used to detect the interaction between CAPZA1 and actin filaments. Finally, a small animal magnetic resonance imager (MRI) was used to observe metastases in HCC cell xenografts in the liver.ResultsCAPZA1 expression levels were negatively correlated with the biological characteristics of primary HCC and patient prognosis. CAPZA1 expression was negatively correlated with the migration and invasion of HCC cells. CAPZA1 down regulation promoted the migration and invasion of HCC cells. Conversely, CAPZA1 overexpression significantly inhibited the migration and invasion of HCC cells. Moreover, CAPZA1 expression levels were correlated with the expression of the EMT markers E-cadherin, N-cadherin and Vimentin. Furthermore, the expression of Snail1 and ZEB1 were negatively correlated with CAPZA1 expression levels. Similarly, CAPZA1 significantly inhibited intrahepatic metastases of HCC cells in an orthotopic transplantation tumour model.ConclusionsCAPZA1 inhibits EMT in HCC cells by regulating actin cytoskeleton remodelling, thereby reducing the metastatic ability of the cells. Together, our data suggest that CAPZA1 could be a useful biomarker for clinical determination of the prognosis of HCC patients.

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Section: Resultsmentioning

confidence: 99%

CAPZA1 modulates EMT by regulating actin cytoskeleton remodelling in hepatocellular carcinoma

Deng

Cao

Zheng

2017

J Exp Clin Cancer Res

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“…The cytoskeleton, composed of the actin cytoskeleton, the microtubule network and the intermediate filaments provide structural design and mechanical strength that is necessary to mold cell shape (8). Although these cytoskeletal components act synergistically, it is the actin cytoskeleton that provides the driving force required for cell migration (9). Thus far, two isoforms, the β-and γ-actins, have been discovered and confirmed to exist in non-muscle cells.…”

Section: Actin Cytoskeletonmentioning

confidence: 99%

Role of cellular cytoskeleton in epithelial-mesenchymal transition process during cancer progression

et al. 2015

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Currently, cancer metastases remain a major clinical problem that highlights the importance of recognition of the metastatic process in cancer diagnosis and treatment. A critical process associated with the metastasis process is the transformation of epithelial cells toward the motile mesenchymal state, a process called epithelial-mesenchymal transition (EMT). Increasing evidence suggests the crucial role of the cytoskeleton in the EMT process. The cytoskeleton is composed of the actin cytoskeleton, the microtubule network and the intermediate filaments that provide structural design and mechanical strength that is necessary for the EMT. The dynamic reorganization of the actin cytoskeleton is a prerequisite for the morphology, migration and invasion of cancer cells. The microtubule network is the cytoskeleton that provides the driving force during cell migration. Intermediate filaments are significantly rearranged, typically switching from cytokeratin-rich to vimentin-rich networks during the EMT process, accompanied by a greatly enhanced cell motility capacity. In the present review, the recent novel insights into the different cytoskeleton underlying EMT are summarized. There are numerous advances in our understanding of the fundamental role of the cytoskeleton in cancer cell invasion and migration.

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“…For example, cancer cells have altered migration rates compared to non-cancer cells from the same tissue. Changes in migration velocity can result from underlying cytoskeletal changes such as shortening of F-actin filaments 35 or from changes in complex biochemical pathways e.g., aberrant androgen signaling in prostate cancer results in altered cell migration. 36 Cell spreading is another actin-dependent feature related to cellular invasiveness.…”

Section: Molecular Phenotypic Biomarkersmentioning

confidence: 99%

Live-single-cell phenotypic cancer biomarkers-future role in precision oncology?

2017

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The promise of precision and personalized medicine is rooted in accurate, highly sensitive, and specific disease biomarkers. This is particularly true for cancer-a disease characterized by marked tumor heterogeneity and diverse molecular signatures. Although thousands of biomarkers have been described, only a very small number have been successfully translated into clinical use. Undoubtedly, there is need for rapid, quantitative, and more cost effective biomarkers for tumor diagnosis and prognosis, to allow for better risk stratification and aid clinicians in making personalized treatment decisions. This is particularly true for cancers where specific biomarkers are either not available (e.g., renal cell carcinoma) or where current biomarkers tend to classify individuals into broad risk categories unable to accurately assess individual tumor aggressiveness and adverse pathology potential (e.g., prostate cancer), thereby leading to problems of over-diagnosis and over-treatment of indolent cancer and under-treatment of aggressive cancer. This perspective highlights an emerging class of cancer biomarkers-live-single-cell phenotypic biomarkers, as compared to genomic biomarkers, and their potential application for cancer diagnosis, risk-stratification, and prognosis.

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The Acetylenic Tricyclic Bis(cyano enone), TBE-31 Inhibits Non–Small Cell Lung Cancer Cell Migration through Direct Binding with Actin

Cited by 15 publications

References 48 publications

CAPZA1 modulates EMT by regulating actin cytoskeleton remodelling in hepatocellular carcinoma

CAPZA1 modulates EMT by regulating actin cytoskeleton remodelling in hepatocellular carcinoma

Role of cellular cytoskeleton in epithelial-mesenchymal transition process during cancer progression

Live-single-cell phenotypic cancer biomarkers-future role in precision oncology?

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