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Source: Oncotarget
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Total 624 results found since Jan 2013.
A switch from CD44+ cell to EMT cell drives the metastasis of prostate cancer.
Authors: Shang Z, Cai Q, Zhang M, Zhu S, Ma Y, Sun L, Jiang N, Tian J, Niu X, Chen J, Sun Y, Niu Y
Abstract
Epithelial-mesenchymal transition (EMT) has been linked to cancer stem-like (CD44+) cell in the prostate cancer (PCa) metastasis. However, the molecular mechanism remains elusive. Here, we found EMT contributed to metastasis in PCa patients failed in androgen deprivation therapy (ADT). Castration TRAMP model also proved PCa treated with ADT promoted EMT with increased CD44+ stem-like cells. Switched CD44+ cell to EMT cell is a key step for luminal PCa cell metastasis. Our results also suggested ADT might go t...
Source: Oncotarget - December 12, 2014 Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Claudin-7 promotes the epithelial-mesenchymal transition in human colorectal cancer.
Authors: Philip R, Heiler S, Mu W, Büchler MW, Zöller M, Thuma F
Abstract
In colorectal cancer (CoCa) EpCAM is frequently associated with claudin-7. There is evidence that tumor-promoting EpCAM activities are modulated by the association with claudin-7. To support this hypothesis, claudin-7 was knocked-down (kd) in HT29 and SW948 cells. HT29-cld7kd and SW948-cld7kd cells display decreased anchorage-independent growth and the capacity for holoclone-, respectively, sphere-formation is reduced. Tumor growth is delayed and cld7kd cells poorly metastasize. In line with this, migratory and invasive potential of cld7kd ...
Source: Oncotarget - December 18, 2014 Category: Cancer & Oncology Tags: Oncotarget Source Type: research
The cylindromatosis gene product, CYLD, interacts with MIB2 to regulate notch signalling.
Authors: Rajan N, Elliott RJ, Smith A, Sinclair N, Swift S, Lord CJ, Ashworth A
Abstract
CYLD, an ubiquitin hydrolase, has an expanding repertoire of regulatory roles in cell signalling and is dysregulated in a number of cancers. To dissect CYLD function we used a proteomics approach to identify CYLD interacting proteins and identified MIB2, an ubiquitin ligase enzyme involved in Notch signalling, as a protein which interacts with CYLD. Coexpression of CYLD and MIB2 resulted in stabilisation of MIB2 protein levels and was associated with reduced levels of JAG2, a ligand implicated in Notch signalling. Conversely, g...
Source: Oncotarget - January 10, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Carnosic acid sensitized TRAIL-mediated apoptosis through down-regulation of c-FLIP and Bcl-2 expression at the post translational levels and CHOP-dependent up-regulation of DR5, Bim, and PUMA expression in human carcinoma caki cells.
In this study, we examined whether carnosic acid could sensitize TRAIL-mediated apoptosis in human renal carcinoma Caki cells. We found that carnosic acid markedly induced TRAIL-mediated apoptosis in human renal carcinoma (Caki, ACHN, and A498), and human hepatocellular carcinoma (SK-HEP-1), and human breast carcinoma (MDA-MB-231) cells, but not normal cells (TMCK-1 and HSF). Carnosic acid induced down-regulation of c-FLIP and Bcl-2 expression at the post-translational levels, and the over-expression of c-FLIP and Bcl-2 markedly blocked carnosic acid-induced TRAIL sensitization. Furthermore, carnosic acid induced death rec...
Source: Oncotarget - January 21, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Identification of PAM4 (clivatuzumab)-reactive epitope on MUC5AC: A promising biomarker and therapeutic target for pancreatic cancer.
Authors: Liu D, Chang CH, Gold DV, Goldenberg DM
Abstract
PAM4 is a monoclonal antibody showing high specificity for pancreatic ductal adenocarcinoma (PDAC). Humanized PAM4 labeled with 90Y in combination with low-dose gemcitabine has shown promising therapeutic activity, and is being evaluated in a phase III clinical trial. Prior efforts have suggested that PAM4 potentially reacts with MUC5AC, a secretory mucin expressed de novo in early pancreatic neoplasia and retained throughout disease progression. In present study, we provide further evidence validating MUC5AC as the PAM4 antigen, and locate PAM4-reactive epi...
Source: Oncotarget - January 21, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Screening analysis of ubiquitin ligases reveals G2E3 as a potential target for chemosensitizing cancer cells.
Authors: Schmidt F, Kunze M, Loock AC, Dobbelstein M
Abstract
Cisplatin is widely used against various tumors, but resistance is commonly encountered. By inducing DNA crosslinks, cisplatin triggers DNA damage response (DDR) and cell death. However, the molecular determinants of how cells respond to cisplatin are incompletely understood. Since ubiquitination plays a major role in DDR, we performed a high-content siRNA screen targeting 327 human ubiquitin ligases and 92 deubiquitinating enzymes in U2OS cells, interrogating the response to cisplatin. We quantified γH2AX by immunofluorescence and image analysis as a r...
Source: Oncotarget - January 21, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research
ERp57 modulates STAT3 activity in radioresistant laryngeal cancer cells and serves as a prognostic marker for laryngeal cancer.
This study shows that ERp57 contributes to radioresistance of laryngeal cancer by activating STAT3. Increased ERp57 was associated with the radioresistant phenotype of laryngeal cancer cells. Interestingly, increased interaction between ERp57 and STAT3 was observed in radioresistant cells, compared to the control cells. This physical complex is required for the activation of STAT3 in the radioresistant cells. Among STAT3-regulatory genes, Mcl-1 was predominantly regulated by ERp57. Inhibition of STAT3 activity with a chemical inhibitor or siRNA-mediated depletion of Mcl-1 sensitized radioresistant cells to irradiation, sug...
Source: Oncotarget - January 27, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Targeting miR-381-NEFL axis sensitizes glioblastoma cells to temozolomide by regulating stemness factors and multidrug resistance factors.
In this study, we employed two-dimensional fluorescence differential gel electrophoresis (2-D DIGE) and MALDI-TOF/TOF-MS/MS to identify 27 differentially expressed proteins, including the significantly upregulated neurofilament light polypeptide (NEFL), in glioblastoma cells in which miR-381 expression was inhibited. We identified NEFL as a novel target molecule of miR-381 and a tumor suppressor gene. In human astrocytoma clinical specimens, NEFL was downregulated with increased levels of miR-381 expression. Either suppressing miR-381 or enforcing NEFL expression dramatically sensitized glioblastoma cells to temozolomide (...
Source: Oncotarget - January 27, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research
DCLK1 is a broadly dysregulated target against epithelial-mesenchymal transition, focal adhesion, and stemness in clear cell renal carcinoma.
Authors: Weygant N, Qu D, May R, Tierney RM, Berry WL, Zhao L, Agarwal S, Chandrakesan P, Chinthalapally HR, Murphy NT, Li JD, Sureban SM, Schlosser MJ, Tomasek JJ, Houchen CW
Abstract
Renal clear cell carcinoma (RCC) is the most common type of kidney cancer and the 8th most common cancer overall in the US. RCC survival rates drop precipitously with regional and distant spread and recent studies have demonstrated that RCC presents an epithelial-mesenchymal transition (EMT) phenotype linked to increased recurrence and decreased survival. EMT is a key characteristic of tumor stem cells (TSCs) along with chemo-resista...
Source: Oncotarget - January 27, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Trafficking protein particle complex 6A delta (TRAPPC6∆) is an extracellular plaque-forming protein in the brain.
Authors: Chang JY, Lee MH, Lin SR, Yang LY, Sun HS, Sze CI, Hong Q, Lin YS, Chou YT, Hsu LJ, Jan MS, Gong CX, Chang NS
Abstract
Tumor suppressor WWOX is involved in the progression of cancer and neurodegeneration. Here, we examined whether protein aggregation occurs in the brain of nondemented, middle-aged humans and whether this is associated with WWOX downregulation. We isolated an N-terminal internal deletion isoform, TPC6AΔ, derived from alternative splicing of the TRAPPC6A (TPC6A) gene transcript. TPC6AΔ proteins are present as aggregates or plaques in the extracellular matrix of the brain such as in the cor...
Source: Oncotarget - February 6, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research
RASSF10 suppresses colorectal cancer growth by activating P53 signaling and sensitizes colorectal cancer cell to docetaxel.
In conclusion, our study demonstrates RASSF10 is frequently methylated in human colorectal cancer leading to loss of expression. RASSF10 normally suppresses human colorectal cancer growth by activating P53 signaling in colorectal cancer, and restored expression sensitizes colorectal cancer to docetaxel.
PMID: 25638156 [PubMed - as supplied by publisher]
Source: Oncotarget - February 6, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Haploinsufficiency of the c-myc transcriptional repressor FIR, as a dominant negative-alternative splicing model, promoted p53-dependent T-cell acute lymphoblastic leukemia progression by activating Notch1.
In conclusion, the alternative splicing of FIR, which generates FIRΔexon2, may contribute to both colorectal carcinogenesis and leukemogenesis.
PMID: 25671302 [PubMed - as supplied by publisher]
Source: Oncotarget - February 13, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Activating enhancer-binding protein-2α induces cyclooxygenase-2 thus promoting nasopharyngeal carcinoma growth.
Authors: Shi D, Xiao X, Tian Y, Qin L, Xie F, Sun R, Wang J, Li W, Liu T, Xiao Y, Yu W, Guo W, Xiong Y, Qiu H, Kang T, Huang W, Zhao C, Deng W
Abstract
Activating enhancer-binding protein-2α (AP-2α) regulates the expression of many cancer-related genes. Here, we demonstrated a novel mechanism by which AP-2α up-regulated cyclooxygenase-2 (COX-2) expression to promote the growth of nasopharyngeal carcinomas (NPCs). High expression of AP-2α in NPC cell lines and tumor tissues from NPC patients was detected and significantly correlated with COX-2 expression. Overexpression of AP-2α and COX-2 in tumor tissues was a...
Source: Oncotarget - February 13, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Hepatitis B virus X protein induces expression of alpha-fetoprotein and activates PI3K/mTOR signaling pathway in liver cells.
In this study, we investigated the regulatory impact of AFP expression on HBx-mediated malignant transformation of human hepatocytes. We found that HBV induced the expression of AFP before that of oncogenes, e.g., Src, Ras and chemokine (C-X-C motif) receptor 4 (CXCR4), and AFP activated protein kinase B (AKT) and mammalian target of rapamycin (mTOR) in HBV-related HCC tissues and in human liver cells transfected with HBx. Cytoplasmic AFP interacted with and inhibited phosphatase and tensin homolog deleted on chromosome 10 (PTEN), activating the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway and promoting mTOR-...
Source: Oncotarget - February 18, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Myeloid differentiation primary response gene 88-leukotriene B4 receptor 2 cascade mediates lipopolysaccharide-potentiated invasiveness of breast cancer cells.
In this study, we showed that LPS upregulated the expression of leukotriene B4 receptor-2 (BLT2) and the synthesis of BLT2 ligands in MDA-MB-231 and MDA-MB-435 breast cancer cells, thereby promoting invasiveness. BLT2 depletion with siRNA clearly attenuated LPS-induced invasiveness. In addition, we demonstrated that myeloid differentiation primary response gene 88 (MyD88) lies upstream of BLT2 in LPS-potentiated invasiveness and that this 'MyD88-BLT2' cascade mediates activation of NF-κB and the synthesis of IL-6 and IL-8, which are critical for the invasiveness and aggression of breast cancer cells. LPS-driven metastasis...
Source: Oncotarget - February 21, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research
