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1.
Sci Rep ; 7(1): 3769, 2017 06 19.
Article in English | MEDLINE | ID: mdl-28630428

ABSTRACT

Symplekin is a multifunctional protein that localizes to both tight junctions and the nucleus in polarized epithelial cells, with confirmed roles in mRNA maturation, transcriptional modulation and tight-junction assembly. However, the mechanisms governing its subcellular distribution and related functions remain unclear. In this study, we found that symplekin primarily localizes to the nuclei of cultured dedifferentiated colorectal cancer cells, and nuclear symplekin showed higher phosphorylation and binding affinity with YBX3 than its membrane fraction. Moreover, the accumulation of nuclear symplekin promoted cell proliferation and dedifferentiation as well as ß-catenin transactivation in vitro. Nuclear symplekin acts as a transcriptional co-activator for the expression of many cell cycle-related genes. Furthermore, extracellular signal-regulated kinase (ERK) phosphorylated symplekin at T1257 to facilitate its nuclear accumulation upon epidermal growth factor (EGF) stimulation. Meanwhile, reduction of total symplekin also induced certain epithelial-mesenchymal transition features in HT-29 cells. Taken together, our results confirm the coordinated roles of symplekin in cell junctions and gene transcription, which are related to its subcellular localization. The significance of nuclear symplekin in tumorigenesis is also highlighted, and ERK-dependent phosphorylation represents a mechanism for its subcellular sorting.


Subject(s)
Cell Nucleus/metabolism , Cell Proliferation , Colorectal Neoplasms/metabolism , MAP Kinase Signaling System , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Neoplasm Proteins/metabolism , Nuclear Proteins/metabolism , Active Transport, Cell Nucleus , Caco-2 Cells , Cell Dedifferentiation , Cell Nucleus/pathology , Colorectal Neoplasms/pathology , Humans
2.
Crit Care ; 17(5): R230, 2013 Oct 10.
Article in English | MEDLINE | ID: mdl-24112558

ABSTRACT

INTRODUCTION: The relationship between admission time and intensive care unit (ICU) mortality is inconclusive and influenced by various factors. This study aims to estimate the effect of admission time on ICU outcomes in a tertiary teaching hospital in China by propensity score matching (PSM) and stratified analysis. METHODS: A total of 2,891 consecutive patients were enrolled in this study from 1 January 2009 to 29 December 2011. Multivariate logistic regression and survival analysis were performed in this retrospective study. PSM and stratified analysis were applied for confounding factors, such as Acute Physiology and Chronic Health Evaluation II (APACHE II) score and admission types. RESULTS: Compared with office hour subgroup (n = 2,716), nighttime (NT, n = 175) subgroup had higher APACHE II scores (14 vs. 8, P < 0.001), prolonged length of stay in the ICU (42 vs. 24 h, P = 0.011), and higher percentages of medical (8.6% vs. 3.3%, P < 0.001) and emergency (59.4% vs. 12.2%, P < 0.001) patients. Moreover, NT admissions were related to higher ICU mortality [odds ratio (OR), 1.725 (95% CI 1.118-2.744), P = 0.01] and elevated mortality risk at 28 days [14.3% vs. 3.2%; OR, 1.920 (95% CI 1.171-3.150), P = 0.01]. PSM showed that admission time remained related to ICU outcome (P = 0.045) and mortality risk at 28 days [OR, 2.187 (95% CI 1.119-4.271), P = 0.022]. However, no mortality difference was found between weekend and workday admissions (P = 0.849), even if weekend admissions were more related to higher APACHE II scores compared with workday admissions. CONCLUSIONS: NT admission was associated with poor ICU outcomes. This finding may be related to shortage of onsite intensivists and qualified residents during NT. The current staffing model and training system should be improved in the future.


Subject(s)
Hospital Mortality , Intensive Care Units , Patient Admission/statistics & numerical data , APACHE , Aged , China/epidemiology , Female , Humans , Male , Middle Aged , Propensity Score
3.
Asian J Androl ; 11(1): 69-73, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19050686

ABSTRACT

Advanced prostate cancer is responsive to hormone therapy that interferes with androgen receptor (AR) signalling. However, the effect is short-lived, as nearly all tumours progress to a hormone-refractory (HR) state, a lethal stage of the disease. Intuitively, the AR should not be involved because hormone therapy that blocks or reduces AR activity is not effective in treating HR tumours. However, there is still a consensus that AR plays an essential role in HR prostate cancer (HRPC) because AR signalling is still functional in HR tumours. AR signalling can be activated in HR tumours through several mechanisms. First, activation of intracellular signal transduction pathways can sensitize the AR to castrate levels of androgens. Also, mutations in the AR can change AR ligand specificity, thereby allowing it to be activated by non-steroids or anti-androgens. Finally, overexpression of the wild-type AR sensitizes itself to low concentrations of androgens. Therefore, drugs targeting AR signalling could still be effective in treating HRPC.


Subject(s)
Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/physiopathology , Receptors, Androgen/physiology , Androgen Antagonists/therapeutic use , Androgens/physiology , Humans , Ligands , Male , Signal Transduction/physiology
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