Pancreatic cancer cells overexpress gelsolin family-capping proteins, which contribute to their cell motility

Thompson, Christopher C.; Ashcroft, Felicity; Patel, S.; Saraga, G; Vimalachandran, Dale; Prime, Wendy; Campbell, Fiona; Dodson, Andrew; Jenkins, Rosalind E.; Lemoine, Nicholas R.; Crnogorac‐Jurčević, Tatjana; Yin, Helen L.; Costello, Eithne

doi:10.1136/gut.2005.083691

Cited by 119 publications

(117 citation statements)

References 31 publications

(38 reference statements)

Supporting

Mentioning

101

Contrasting

Unclassified

Order By: Relevance

“…3,20,25,30 On the other hand, the knockdown using siRNA in carcinoma cells constitutively overexpressing endogenous CapG impairs cell motility. 22 In our model cell lines, we observe a distribution of the CapGeGFP fusion protein in the living cells, which is concurrent with the reported distribution in fixed and immunostained cells. The invasiveness of the MDA-MB-231 expressing CapG-eGFP is siRNA molecules at end concentration of 2.5 nM each in a total of 2 ml medium reduce invasiveness to 70.6% 6 2.2%; 5 nM: siRNA molecules at end concentration of 5 nM each in a total of 2 ml medium reduce invasiveness to 92.7% 6 2.3%.…”

Section: Capg Knockdown Reduces Invasivenesssupporting

confidence: 71%

“…Further correlations between immunohisto-chemical staining and established prognostic parameters could not be verified. 22 A few lung-and stomach cancer cell lines and a melanoma cell line were reported, however, to be deficient in CapG, in contrast to the corresponding normal tissues. 25 In summary, the involvement of CapG in cell motility and in particular in metastasis led us to investigate its dynamical distribution in the living cell.…”

mentioning

confidence: 99%

“…In ovarian and pancreatic cancer, in glioblastoma and in ocular melanoma an overexpression of the protein was described as well. [21][22][23][24] Regarding pancreatic cancer, the intensity of immunohistochemical staining of CapG within the cell nucleus appears to be correlated with tumor size. Further correlations between immunohisto-chemical staining and established prognostic parameters could not be verified.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Invasive breast cancer cells exhibit increased mobility of the actin‐binding protein CapG

Renz

Betz

Niederacher

et al. 2008

Intl Journal of Cancer

View full text Add to dashboard Cite

The CapG protein, a Gelsolin-related actin-binding protein, is expressed at higher levels in breast cancer, especially in metastasizing breast cancer, than in normal breast epithelium. Furthermore, it is known that an increased expression of the CapG protein triggers an increase in cell motility. According to in vitro experiments, it was supposed that it is the nuclear fraction of the protein, which causes the increase in cell motility. Here, we examined the dynamical distribution of the CapG protein within the living cell, i.e. the import of the CapG protein into the nucleus. The nuclear import kinetics of invasive, metastasizing breast cancer cells were compared to the import kinetics of non-neoplastic cells similar to normal breast epithelium. FRAP kinetics showed a highly significant increase in the recovery of photobleached CapG-eGFP in the cancer cells, so that a differentiation of invasive, metastasizing cells and non-invasive, non-metastasizing cells on the basis of transport processes of the CapG protein between the nucleus and the cytoplasm seems to be possible. Comprehension of the mobility and compartmentalization of the CapG protein in normal and in cancer cells in vivo could constitute a new basis to characterize the invasiveness and metastasizing potential of breast cancer. ' 2007 Wiley-Liss, Inc.

show abstract

Section: Capg Knockdown Reduces Invasivenesssupporting

confidence: 71%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Invasive breast cancer cells exhibit increased mobility of the actin‐binding protein CapG

Renz

Betz

Niederacher

et al. 2008

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…Knockout of CapG causes membrane ruffling and phagocytosis defects in macrophages and motility defects in neutrophil granulocytes and dendritic cells (Parikh et al 2003), whereas its overexpression triggers an increase in cell motility of various benign cells (fibroblasts (Sun et al 1995), endothelial cells (Pellieux et al 2003) and kidney cells of the dog (De Corte et al 2004)). Some authors refer to the Festablished role of CapG in physiological motility of benign cells_ (Thompson et al 2007).…”

Section: Known Capg Propertiesmentioning

confidence: 99%

Dynamics of the CapG actin-binding protein in the cell nucleus studied by FRAP and FCS

Renz

Langowski

2008

Chromosome Res

View full text Add to dashboard Cite

FRAP (fluorescence recovery after photobleaching) and FCS (fluorescence correlation spectroscopy) are spectroscopic methods for monitoring the dynamic distribution of proteins inside the nucleus of living cells. As an example we report our studies on the intracellular mobility of the actin-binding protein CapG in live breast cancer cells. This Gelsolin-related protein is a putative oncogene. It appears to be overexpressed especially in metastasizing breast cancer. Furthermore, the CapG protein is known to be involved in the motility control of non-muscle benign cells. Its increased expression triggers an increase in cell motility of benign cells. Thus it can be expected that in cancer cells overexpressing the CapG protein, motility, invasiveness and metastasis might be particularly promoted. Since the nuclear CapG fraction seems to be pivotal to the increase in cell motility, we focused our studies on the CapG mobility in cell nuclei of live breast cancer cells. Using FCS and FRAP we showed that the eGFP-tagged CapG is monomeric and characterized its diffusional properties on the microsecond to minute timescale. This information about the mobility and compartmentalization of CapG might help to provide insight into its function within the cell nucleus and give clues about its altered cellular function in malignant dedifferentiation. Abbreviations ACF autocorrelation function CapGGelsolin-related actin binding capping protein CapG-eGFP CapG-eGFP fusion protein eGFP enhanced green fluorescent protein FCS fluorescence correlation spectroscopy FRAP fluorescence recovery after photobleaching NLS nuclear localization signal PI 3-kinase phosphatidylinositol 3-hydroxy kinase PIP 2 -binding phospatidylinositol 4,5-bisphosphate

show abstract

“…CapG was originally isolated from the cytoplasm of alveolar macrophages and has been shown to be involved in the control of actin-based cell motility and membrane ruffling (phagocytosis) of nonmuscle cells. It also functions as a nuclear actin-binding protein to prevent nuclear actin from polymerizing and to keep it in a monomeric globular or short oligomeric form (Thompson et al, 2007;Renz et al, 2008). There are currently no studies in the literature examining the role of CapG in NSCLC.…”

mentioning

confidence: 99%

Prognostic Evaluation of CapG, Gelsolin, P‐gp, GSTP1, and Topo‐II Proteins in Non‐Small Cell Lung Cancer

Zhu

Hunag

Liu

et al. 2011

The Anatomical Record

View full text Add to dashboard Cite

Metastasis and multidrug resistance (MDR) are the main reasons for the poor prognosis of non-small cell lung cancer (NSCLC) patients. The use of biomarkers may contribute to a more accurate prediction of tumor metastasis, a better response to chemotherapy, and better patient survival. Gelsolin-like actin-capping protein (CapG) and gelsolin have been identified as playing important roles in tumor invasion and metastasis. Permeability glycoprotein (P-gp), glutathione S-transferase pi (GSTP1), and topoisomerase-II (Topo-II) are proteins that are closely related to MDR. In this study, we assessed the prognostic significance of CapG and gelsolin (both markers of tumor motility), and of P-gp, GSTP1, and Topo-II (markers of MDR) in NSCLC patients. One hundred and twenty-one patients with pathologically confirmed, resectable NSCLC were included in the study. The expression levels of the five kinds of proteins mentioned above were determined by immunohistochemistry (IHC). The correlation between the clinical characteristics and IHC findings were analyzed. Expression of CapG, gelsolin, and P-gp was found to be associated with an increased risk of death (Hazard Ratio (HR) ¼ 2.799, 95% Confidence Interval (CI) ¼ 1.2705-6.169, P ¼ 0.011; HR ¼ 3.968, 95% CI ¼ 1.811-8.693, P ¼ 0.001; HR ¼ 3.251, 95% CI ¼ 1.456-7.260, P ¼ 0.004, respectively), whereas expression of GSTP1 and Topo-II was not. These results suggest that higher tumor motility and MDR may be important in NSCLC prognosis. Anat Rec, 295:208-214, 2012. V V C 2011 Wiley Periodicals, Inc.Key words: NSCLC; CapG; gelsolin; P-gp; prognosisLung cancer remains the leading cause of cancerrelated deaths in China, in both males and females. The most common form of lung cancer, non-small cell lung cancer (NSCLC), has a 5-year relative survival rate below 70% in patients with Stage I tumors, and below 1% in patients with Stage IV tumors (Jemal et al., 2009). Treatment of patients with NSCLC is governed by various prognostic factors such as surgical stage, histological grade, differentiation, and lymph node metastasis. Nevertheless, the clinical outcome in individual patients is often difficult to predict.The main cause of death from lung cancer is usually related to metastasis and resistance to chemotherapeutics after primary surgery. If prognosis could be determined more precisely before treatment, then patients would be more effectively treated with individualized therapy. Compared with mRNAs, which degrade quickly if samples are not prepared correctly, proteins are more stable and potentially very useful biomarkers. Furthermore, differences in protein expression may reveal information about biological properties of tumors.

show abstract

Pancreatic cancer cells overexpress gelsolin family-capping proteins, which contribute to their cell motility

Cited by 119 publications

References 31 publications

Invasive breast cancer cells exhibit increased mobility of the actin‐binding protein CapG

Invasive breast cancer cells exhibit increased mobility of the actin‐binding protein CapG

Dynamics of the CapG actin-binding protein in the cell nucleus studied by FRAP and FCS

Prognostic Evaluation of CapG, Gelsolin, P‐gp, GSTP1, and Topo‐II Proteins in Non‐Small Cell Lung Cancer

Contact Info

Product

Resources

About