Prognostic value of CAPZA1 overexpression in gastric cancer

Lee, Young-Joon; Jeong, Sang‐Ho; Hong, Soon-Chan; Cho, Bok-Im; Ha, Woo-Song; Park, Soon-Tae; Choi, Sang-Kyung; Jung, Eun-Jung; Ju, Young‐Tae; Jeong, Chi Young; Kim, Jae Won; Lee, Chang Won; Yoo, Ji Myong; Ko, Gyung Hyuck

doi:10.3892/ijo.2013.1867

Cited by 28 publications

(28 citation statements)

References 34 publications

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“…Sun et al reported that changes in CAPZ expression could be used as a diagnostic marker for malignant melanoma [26], and Yu et al observed that CAPZA1 expression was reduced in stage IV neuroblastoma [27]. Lee et al reported that CAPZA1 overexpression was a marker of good prognosis for patients with gastric cancer [14]. However, it should be noted that there have been few studies on the role of CAPZA1 in HCC.…”

Section: Discussionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

“…CAPZA1 encodes the α1 subunit of CAPZ [13] and has been reported to play a role in gastric cancer metastasis. However, neither the role of CAPZA1 in HCC nor the molecular mechanism of CAPZA1 regulation of tumour metastasis has been defined [14]. …”

Section: Introductionmentioning

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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“…Recently, Lee and colleagues reported that CapZA1 expression is associated with decreased cancer cell migration and invasion and could be used as a good prognostic marker of gastric cancer (44). The authors also showed that CapZA1 depletion causes a significant increase in gastric cancer cell migration and invasion, whereas CapZA1 overexpression shows the opposite effects.…”

Section: Tnks1bp1 As a Possible Regulator Of Cancer Invasionmentioning

confidence: 99%

Tankyrase-Binding Protein TNKS1BP1 Regulates Actin Cytoskeleton Rearrangement and Cancer Cell Invasion

et al. 2017

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Tankyrase, a PARP that promotes telomere elongation and Wnt/b-catenin signaling, has various binding partners, suggesting that it has as-yet unidentified functions. Here, we report that the tankyrase-binding protein TNKS1BP1 regulates actin cytoskeleton and cancer cell invasion, which is closely associated with cancer progression. TNKS1BP1 colocalized with actin filaments and negatively regulated cell invasion. In TNKS1BP1-depleted cells, actin filament dynamics, focal adhesion, and lamellipodia ruffling were increased with activation of the ROCK/LIMK/cofilin pathway. TNKS1BP1 bound the actin-capping protein CapZA2. TNKS1BP1 depletion dissociated CapZA2 from the cytoskeleton, leading to cofilin phosphorylation and enhanced cell invasion. Tankyrase overexpression increased cofilin phosphorylation, dissociated CapZA2 from cytoskeleton, and enhanced cell invasion in a PARP activitydependent manner. In clinical samples of pancreatic cancer, TNKS1BP1 expression was reduced in invasive regions. We propose that the tankyrase-TNKS1BP1 axis constitutes a posttranslational modulator of cell invasion whose aberration promotes cancer malignancy. Cancer Res; 77(9); 2328-38. Ó2017 AACR.

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“…Cytoskeleton proteins play an important role in this process; for example, CAPZA1 interacts with cytoskeletal actin. Lee et al 21 found that CAPZA1 is a marker for a good prognosis in GC and is associated with the decreased migration and invasion of cancer cells. Liu et al 47 reported that Scinderin inhibited the formation of filopodia and decreased the expression of CDC42 along with GC cell migration.…”

Section: Discussionmentioning

confidence: 99%

“…Two siRNA oligos against CD2AP and CAPZA1 were designed (siCD2AP‐1: 5′‐GTG GAA CCC TGA ATA ACA A‐3′/siCD2AP‐2: 5′‐ GGG CGA ACT TAA TGG TAA A‐3′, and siCAPZA1: 5′‐CUG UGA AGA UAG AAG GAU‐3′) 21 and synthesized by RiboBio (Guangzhou, China). The siRNAs were transfected into GC cells at a final concentration of 20 nM using Lipofectamine 2000 reagent (Invitrogen, Carlsbad, CA).…”

Section: Methodsmentioning

confidence: 99%

CD2AP inhibits metastasis in gastric cancer by promoting cellular adhesion and cytoskeleton assembly

Xie

Chen

Zheng

et al. 2020

Molecular Carcinogenesis

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Diffuse gastric cancer (DGC) is a lethal malignancy lacking effective systemic therapy. Among the most provocative recent results in DGC has been that the alter of the cellular cytoskeleton and intercellular adhesion. CD2‐associated protein (CD2AP) is one of the critical proteins regulating cytoskeleton assembly and intercellular adhesion. However, no study has investigated the expression and biological significance of CD2AP in gastric cancer (GC) to date. Therefore, the aim of our study was to explore if the expression of CD2AP is associated with any clinical features of GC and to elucidate the underlying mechanism. Immunohistochemistry of 620 patient tissue samples indicated that the expression of CD2AP is downregulated in DGC. Moreover, a low CD2AP level was indicative of poor patient prognosis. In vitro, forced expression of CD2AP caused a significant decrease in the migration and invasion of GC cells, whereas depletion of CD2AP had the opposite effect. Immunofluorescence analysis indicated that CD2AP promoted cellular adhesion and influenced cell cytoskeleton assembly via interaction with the F‐actin capping protein CAPZA1. Overall, the upregulation of CD2AP could attenuate GC metastasis, suggesting CD2AP as a novel biomarker for the prognosis and treatment of patients with GC.

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Prognostic value of CAPZA1 overexpression in gastric cancer

Cited by 28 publications

References 34 publications

CAPZA1 modulates EMT by regulating actin cytoskeleton remodelling in hepatocellular carcinoma

CAPZA1 modulates EMT by regulating actin cytoskeleton remodelling in hepatocellular carcinoma

Tankyrase-Binding Protein TNKS1BP1 Regulates Actin Cytoskeleton Rearrangement and Cancer Cell Invasion

CD2AP inhibits metastasis in gastric cancer by promoting cellular adhesion and cytoskeleton assembly

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