FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1993091794> ?p ?o ?g. }

• W1993091794 endingPage "1004" @default.
• W1993091794 startingPage "1002" @default.
• W1993091794 abstract "To the Editor:Lung cancer currently remains the leading cause of cancer-related deaths because of its aggressive nature. The 5-year survival rates for localized and regional disease are 54 and 26%, respectively, but only 4% for patients with late-stage (stage IV) disease (1). Thus, development of biomarkers to identify patients at high risk for aggressive progression is of urgent need. Recently, we have reported myristoylated alanine-rich C kinase substrate (MARCKS), predominantly its phosphorylated state, as a risk factor associated with lung cancer invasiveness and metastasis (2). MARCKS is a substrate of protein kinase C, and also a membrane-associated protein. Upon phosphorylation at Ser159 and Ser163 within its phosphorylation site domain, phosphorylated MARCKS (phospho-MARCKS) is detached from the plasma membrane and is able to regulate various cellular processes, including cell migration and exocytic vesicle release (2–4). In the lungs, MARCKS has been extensively studied because of its role in regulating mucus secretion and inflammation. Inhibition of MARCKS activity not only reduces airway mucus hypersecretion both in vitro and in vivo (3, 5), but also represses inflammatory leukocyte migration and degranulation (6, 7). There have been limited studies on MARCKS in cancer metastasis, but the results have been conflicting (8–13). This is because MARCKS expression is ubiquitous in various normal and tumor tissues. Despite this, there is a consensus that phospho-MARCKS, a post-translational modification, is associated with cell motility, and has a role in the regulation of cancer cell invasiveness and metastasis (2, 4, 14, 15). Of note, our laboratory discovered that inhibition of MARCKS phosphorylation was able to reduce lung cancer metastasis in murine models (2). However, the clinical significance of phospho-MARCKS in different cancers remains to be determined. In particular, there is limited information regarding its relevance in cancer progression, especially lung cancer.Based on 18 pairs of normal and malignant lung cancer tissue sections, we previously reported that elevated phospho-MARCKS was seen in malignant lung cancer tissue sections, but not in their adjacent normal counterparts (2), suggesting a potential association between MARCKS phosphorylation and more aggressive lung cancer histological grades. To investigate more fully this previous finding, we analyzed samples from a cohort of 110 human patients with lung cancer using immunohistochemical staining with an anti-pSer159/163 MARCKS monoclonal antibody (see the online supplement). The clinical characteristics of these patients are summarized in Table 1. Consistent with our previous reports (2), high levels of MARCKS phosphorylation were found in tumor tissues compared with normal lung tissues (Figures 1A–1F). Weak phospho-MARCKS staining was observed in the cytoplasm of lung cancer tissue samples from patients in stage I (Figure 1C). In contrast, strong MARCKS phosphorylation occurred in advanced-stage lung cancer tissue samples (Figures 1D–1F). The levels of MARCKS phosphorylation correlated significantly with advanced stages of disease (Figure 1G, Pearson’s chi-square test).Table 1:Phosphorylated Myristoylated Alanine-Rich C Kinase Substrate Levels in Relation to Clinicopathologic Characteristics of Patients with Non–Small Cell Lung Cancer*Figure 1.High phosphorylated myristoylated alanine-rich C kinase substrate (phospho-MARCKS) levels correlate with advanced stages, lymph node metastasis, and invasion of lung cancer. (A–F) Representative images of immunohistochemical staining using anti-pSer159/163 ...To quantitatively investigate these impressions, bivariate logistic regression models to predict the likelihood of high phospho-MARCKS levels from advanced tumor stages were estimated, and the probabilities of high phospho-MARCKS with stage I to III are shown in Figure 1H. The analyses demonstrated that, for a one-unit increase in stages II and III, the log odds of high expression of phospho-MARCKS levels increased by 1.00 and 2.46 compared with stage I. There were significant differences in the logistic probabilities of high phospho-MARCKS levels between stages I and II (P = 0.039), as well as stages I and III (P < 0.001), respectively. These results suggest that phospho-MARCKS may be a promising clinical predictor of tumor stages in patients with lung cancer.Moreover, we also investigated the significance of phospho-MARCKS in lymph node status and found that higher levels of MARCKS phosphorylation correlated with lymph node metastasis (Figure 1I, N0 versus N1–2). Notably, MARCKS phosphorylation was lower in a subtype of adenocarcinoma, bronchoalveolar carcinoma, which shows a less invasive phenotype than adenocarcinoma (Figure 1J, AC versus bronchoalveolar carcinoma). Because tumor necrosis is a common event in aggressive cancers, we further checked phospho-MARCKS levels in the 10 tumor tissues with necrosis in this set of tissue arrays. Interestingly, we found higher staining intensity and increased numbers of cells stained with anti–phospho-MARCKS antibody in these tumors. These data raise the possibility that high phospho-MARCKS levels may contribute to cancer progression in non–small cell lung cancers, and the detection of phospho-MARCKS could potentially be used as a prognostic biomarker for the disease.In this correspondence, we demonstrate that higher MARCKS phosphorylation is correlated with lung cancer in advanced stages (stage II–IV), lymph node metastatic status, and malignant phenotypes. In addition to our previously published results (2), the current work further confirms the importance of phospho-MARCKS in driving the progression of lung cancer toward more malignancy, suggesting that phospho-MARCKS levels may determine the progression of localized lung cancer toward late stage. Taken together, high phospho-MARCKS levels appear to confer cancer malignancy, and may serve as a novel biomarker. Inhibition of MARCKS phosphorylation, the post-translational step, may be an effective strategy for controlling lung cancer progression." @default.
• W1993091794 created "2016-06-24" @default.
• W1993091794 creator A5036513445 @default.
• W1993091794 creator A5049792656 @default.
• W1993091794 creator A5053024002 @default.
• W1993091794 creator A5081860028 @default.
• W1993091794 date "2014-04-15" @default.
• W1993091794 modified "2023-09-30" @default.
• W1993091794 title "A Novel Predictor of Cancer Malignancy: Up-regulation of Myristoylated Alanine-Rich C Kinase Substrate Phosphorylation in Lung Cancer" @default.
• W1993091794 cites W1653041927 @default.
• W1993091794 cites W1966229686 @default.
• W1993091794 cites W1975854261 @default.
• W1993091794 cites W2007491631 @default.
• W1993091794 cites W2034532358 @default.
• W1993091794 cites W2041366399 @default.
• W1993091794 cites W2057312796 @default.
• W1993091794 cites W2082796322 @default.
• W1993091794 cites W2124117141 @default.
• W1993091794 cites W2124145066 @default.
• W1993091794 cites W2124439357 @default.
• W1993091794 cites W2156553708 @default.
• W1993091794 cites W2169961966 @default.
• W1993091794 doi "https://doi.org/10.1164/rccm.201401-0053le" @default.
• W1993091794 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4098099" @default.
• W1993091794 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24735036" @default.
• W1993091794 hasPublicationYear "2014" @default.
• W1993091794 type Work @default.
• W1993091794 sameAs 1993091794 @default.
• W1993091794 citedByCount "16" @default.
• W1993091794 countsByYear W19930917942014 @default.
• W1993091794 countsByYear W19930917942015 @default.
• W1993091794 countsByYear W19930917942016 @default.
• W1993091794 countsByYear W19930917942017 @default.
• W1993091794 countsByYear W19930917942019 @default.
• W1993091794 countsByYear W19930917942020 @default.
• W1993091794 countsByYear W19930917942021 @default.
• W1993091794 countsByYear W19930917942022 @default.
• W1993091794 crossrefType "journal-article" @default.
• W1993091794 hasAuthorship W1993091794A5036513445 @default.
• W1993091794 hasAuthorship W1993091794A5049792656 @default.
• W1993091794 hasAuthorship W1993091794A5053024002 @default.
• W1993091794 hasAuthorship W1993091794A5081860028 @default.
• W1993091794 hasBestOaLocation W19930917942 @default.
• W1993091794 hasConcept C11960822 @default.
• W1993091794 hasConcept C121608353 @default.
• W1993091794 hasConcept C126322002 @default.
• W1993091794 hasConcept C143998085 @default.
• W1993091794 hasConcept C184235292 @default.
• W1993091794 hasConcept C2776256026 @default.
• W1993091794 hasConcept C2779399171 @default.
• W1993091794 hasConcept C2779856020 @default.
• W1993091794 hasConcept C502942594 @default.
• W1993091794 hasConcept C515207424 @default.
• W1993091794 hasConcept C55493867 @default.
• W1993091794 hasConcept C71924100 @default.
• W1993091794 hasConcept C86803240 @default.
• W1993091794 hasConcept C95444343 @default.
• W1993091794 hasConceptScore W1993091794C11960822 @default.
• W1993091794 hasConceptScore W1993091794C121608353 @default.
• W1993091794 hasConceptScore W1993091794C126322002 @default.
• W1993091794 hasConceptScore W1993091794C143998085 @default.
• W1993091794 hasConceptScore W1993091794C184235292 @default.
• W1993091794 hasConceptScore W1993091794C2776256026 @default.
• W1993091794 hasConceptScore W1993091794C2779399171 @default.
• W1993091794 hasConceptScore W1993091794C2779856020 @default.
• W1993091794 hasConceptScore W1993091794C502942594 @default.
• W1993091794 hasConceptScore W1993091794C515207424 @default.
• W1993091794 hasConceptScore W1993091794C55493867 @default.
• W1993091794 hasConceptScore W1993091794C71924100 @default.
• W1993091794 hasConceptScore W1993091794C86803240 @default.
• W1993091794 hasConceptScore W1993091794C95444343 @default.
• W1993091794 hasIssue "8" @default.
• W1993091794 hasLocation W19930917941 @default.
• W1993091794 hasLocation W19930917942 @default.
• W1993091794 hasLocation W19930917943 @default.
• W1993091794 hasLocation W19930917944 @default.
• W1993091794 hasOpenAccess W1993091794 @default.
• W1993091794 hasPrimaryLocation W19930917941 @default.
• W1993091794 hasRelatedWork W1964515703 @default.
• W1993091794 hasRelatedWork W1967103478 @default.
• W1993091794 hasRelatedWork W2032912323 @default.
• W1993091794 hasRelatedWork W2051108283 @default.
• W1993091794 hasRelatedWork W2294235576 @default.
• W1993091794 hasRelatedWork W2372561159 @default.
• W1993091794 hasRelatedWork W2375344515 @default.
• W1993091794 hasRelatedWork W2390152934 @default.
• W1993091794 hasRelatedWork W2889373858 @default.
• W1993091794 hasRelatedWork W3005884874 @default.
• W1993091794 hasVolume "189" @default.
• W1993091794 isParatext "false" @default.
• W1993091794 isRetracted "false" @default.
• W1993091794 magId "1993091794" @default.
• W1993091794 workType "article" @default.