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EMT and cancer

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https://www.readbyqxmd.com/read/28719656/phenotypic-characterization-of-circulating-tumor-cells-in-the-peripheral-blood-of-patients-with-small-cell-lung-cancer
#1
Ippokratis Messaritakis, Eleni Politaki, Athanasios Kotsakis, Eleftheria-Kleio Dermitzaki, Filippos Koinis, Eleni Lagoudaki, Anastasios Koutsopoulos, Galatea Kallergi, John Souglakos, Vassilis Georgoulias
BACKGROUND: To evaluate the phenotypic heterogeneity of circulating tumor cells (CTCs) based on the expression of proliferative, apoptotic and Epithelial-to-Mesenchymal Transmission (EMT) markers during front-line treatment in patients with small cell lung cancer (SCLC) and to evaluate their clinical relevance. METHODS: CTCs from 108 chemotherapy-naïve patients with SCLC were analyzed by double immunofluorescence staining using anti-Ki67, anti-M30, anti-Vimentin along with anti-CKs antibodies...
2017: PloS One
https://www.readbyqxmd.com/read/28719220/egfr-targeted-cationic-polymeric-mixed-micelles-for-co-delivery-of-gemcitabine-and-mir-205-for-treating-advanced-pancreatic-cancer
#2
Goutam Mondal, Saud Almawash, Amit Kumar Chaudhary, Ram I Mahato
Gemcitabine (GEM), a first-line chemotherapy for pancreatic cancer undergoes rapid metabolism and develops chemoresistance after repeated administration. We previously demonstrated that the combination of GEM and miR-205 provides an effective therapeutic strategy to sensitize GEM-resistant pancreatic cancer cells. Since epidermal growth factor receptor (EGFR) is overexpressed in pancreatic cancer cells, in this study, we aimed to deliver mixed micelles containing GEM and miR-205 decorated with EGFR-targeting cetuximab (C225) monoclonal antibody for targeted therapy...
July 18, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28718842/secreted-protein-acidic-and-rich-in-cysteine-sparc-enhances-cell-proliferation-migration-and-epithelial-mesenchymal-transition-and-sparc-expression-is-associated-with-tumor-grade-in-head-and-neck-cancer
#3
Chih-Hau Chang, Meng-Chi Yen, Ssu-Hui Liao, Yu-Ling Hsu, Chung-Sheng Lai, Kao-Ping Chang, Ya-Ling Hsu
Secreted protein acidic and rich in cysteine (SPARC) is a secreted protein which is involved in various biological processes. SPARC expression is associated with tumor metastasis and poor prognosis in several types of cancer. However, the SPARC-induced signaling pathway was not fully understood in head and neck cancer. In this study, our results showed that SPARC treatment promoted cell proliferation and migration in head and neck cancer cell lines FaDu and Detroit 562. In addition, SPARC induced expression of epithelial mesenchymal transition (EMT) regulators, including Slug, Snail, and Twist in Detroit 562...
July 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28717171/the-aspirin-metabolite-salicylate-inhibits-lysine-acetyltransferases-and-muc1-induced-epithelial-to-mesenchymal-transition
#4
Harvey R Fernandez, Sara K Lindén
MUC1 is a transmembrane mucin that can promote cancer progression, and its upregulation correlates with a worse prognosis in colon cancer. We examined the effects of overexpression of MUC1 in colon cancer cells, finding that it induced epithelial to mesenchymal transition (EMT), including enhanced migration and invasion, and increased Akt phosphorylation. When the clones were treated with the aspirin metabolite salicylate, Akt phosphorylation was decreased and EMT inhibited. As the salicylate motif is necessary for the activity of the lysine acetyltransferase (KAT) inhibitor anacardic acid, we hypothesized these effects were associated with the inhibition of KAT activity...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716897/mcpip1-downregulation-in-clear-cell-renal-cell-carcinoma-promotes-vascularization-and-metastatic-progression
#5
Paulina Marona, Judyta Górka, Zofia Mazurek, Waclaw Wilk, Janusz Rys, Marcin Majka, Jolanta Jura, Katarzyna Miekus
<p>Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and it forms highly vascularized tumors. The monocyte endoribonuclease MCPIP1 negatively regulates inflammation by degrading mRNA encoding proinflammatory cytokines, such as IL-6, IL-1 and IL-12. MCPIP1 is also a negative regulator of NFκB and AP1 activity and it influences a broad range of miRNA activities. Here we report that MCPIP1 protein levels are decreased during renal cancer progression. In patient-derived tumors, and xenografts established in NOD-SCID or nude mice, low MCPIP1 levels correlated strongly with increased proliferation, tumor outgrowth and vascularity...
July 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28716573/htra3-stromal-expression-is-correlated-with-tumor-budding-in-stage-ii-colorectal-cancer
#6
Catherine L Forse, Mahdi Rahimi, Eleftherios P Diamandis, Naziheh Assarzadegan, Heather Dawson, Andrea Grin, Erin Kennedy, Brenda O'Connor, David E Messenger, Robert H Riddell, Richard Kirsch, George S Karagiannis
Tumor budding is a well-established adverse prognostic factor in colorectal carcinoma (CRC). It may represent a form of epithelial-to-mesenchymal transition (EMT), although the underlying mechanisms remain unclear. High-temperature requirement A3 (HtrA3) is an inhibitor of the bone morphogenetic protein pathway, the suppression of which has been linked to EMT. Since HtrA3 is highly expressed in the desmoplastic stroma at the CRC invasive front, we sought to evaluate the relationship between tumor budding and HtrA3 expression in 172 stage II CRC resection specimens...
July 14, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28716088/loss-of-dip2c-in-rko-cells-stimulates-changes-in-dna-methylation-and-epithelial-mesenchymal-transition
#7
Chatarina Larsson, Muhammad Akhtar Ali, Tatjana Pandzic, Anders M Lindroth, Liqun He, Tobias Sjöblom
BACKGROUND: The disco-interacting protein 2 homolog C (DIP2C) gene is an uncharacterized gene found mutated in a subset of breast and lung cancers. To understand the role of DIP2C in tumour development we studied the gene in human cancer cells. METHODS: We engineered human DIP2C knockout cells by genome editing in cancer cells. The growth properties of the engineered cells were characterised and transcriptome and methylation analyses were carried out to identify pathways deregulated by inactivation of DIP2C...
July 17, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28716029/foxp3-promotes-tumor-growth-and-metastasis-by-activating-wnt-%C3%AE-catenin-signaling-pathway-and-emt-in-non-small-cell-lung-cancer
#8
Shucai Yang, Yi Liu, Ming-Yue Li, Calvin S H Ng, Sheng-Li Yang, Shanshan Wang, Chang Zou, Yujuan Dong, Jing Du, Xiang Long, Li-Zhong Liu, Innes Y P Wan, Tony Mok, Malcolm J Underwood, George G Chen
BACKGROUND: The role of cancer cell FOXP3 in tumorigenesis is conflicting. We aimed to study FOXP3 expression and regulation, function and clinical implication in human non-small cell lung cancer (NSCLC). METHODS: One hundred and six patients with histologically-confirmed NSCLC who underwent surgery were recruited for the study. Tumor samples and NSCLC cell lines were used to examine FOXP3 and its related molecules. Various cell functions related to tumorigenesis were performed...
July 17, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28716024/mir-661-promotes-tumor-invasion-and-metastasis-by-directly-inhibiting-rb1-in-non-small-cell-lung-cancer
#9
Feiye Liu, Yanjun Cai, Xiaoxiang Rong, Jinzhang Chen, Dayong Zheng, Lu Chen, Junyi Zhang, Rongcheng Luo, Peng Zhao, Jian Ruan
BACKGROUND: Aberrant microRNA expression has been implicated in metastasis of cancers. MiR-661 accelerates proliferation and invasion of breast cancer and ovarian cancer, while impedes that of glioma. Its role in non small cell lung cancer (NSCLC) and underlying mechanism are worthy elucidation. METHODS: Expression of miR-661 was measured with real-time PCR in both NSCLC tissues and cell lines. The effects of miR-661 on migration, invasion and metastasis capacity of NSCLC were evaluated using wound healing, transwell assay and animal models...
July 17, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28716020/long-non-coding-rna-casc2-suppresses-epithelial-mesenchymal-transition-of-hepatocellular-carcinoma-cells-through-casc2-mir-367-fbxw7-axis
#10
Yufeng Wang, Zhikui Liu, Bowen Yao, Qing Li, Liang Wang, Cong Wang, Changwei Dou, Meng Xu, Qingguang Liu, Kangsheng Tu
BACKGROUND: Recently, it has been reported that long non-coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2), a novel tumor suppressor, participates in regulating the carcinogenesis and suppresses tumor progression by sponging microRNAs (miRNAs). However, the expression and function of CASC2 in hepatocellular carcinoma (HCC) remain unclear. METHODS: The expression of CASC2 and miR-367 in HCC specimens and cell lines were detected by real-time PCR. Western blotting and immunohistochemistry were carried out for detection of epithelial-to-mesenchymal transition (EMT) markers in HCC...
July 17, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28714030/kdm5a-promotes-proliferation-and-emt-in-ovarian-cancer-and-closely-correlates-with-ptx-resistance
#11
Tongfu Feng, Yan Wang, Yan Lang, Yuanzhen Zhang
The authors initially performed reverse transcription‑quantitative polymerase chain reaction to determine the expression profile of KDM5A in ovarian cancer tissues and adjacent normal tissue. Compared with adjacent normal tissue, it was identified that KDM5A was highly expressed in ovarian cancer tissues. Moreover, human ovarian cell lines also confirmed that KDM5A was highly expressed in ovarian cancer. KDM5A was especially highly expressed in SKOV3/paclitaxel (PTX) cells, which are resistant to PTX. Previous studies demonstrated that chemoresistance in cancer cells facilitates epithelial‑to‑mesenchymal transition (EMT)...
July 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713970/human-chorionic-gonadotropin%C3%A2-%C3%AE-regulates-epithelial-mesenchymal-transition-and-metastasis-in-human-ovarian-cancer
#12
Na Liu, Shu-Min Peng, Guang-Xi Zhan, Jing Yu, Wei-Min Wu, Hao Gao, Xiao-Feng Li, Xiao-Qing Guo
Human chorionic gonadotropin β (β-hCG) is a well-known and accurate marker for the diagnosis and monitoring of pregnancy, trophoblastic tumors and ovarian germ cell tumors. Recently, β-hCG has been found to be closely related to poor prognosis and metastasis in various other malignant tumors, while its role and mechanism in ovarian cancer is still unclear. In the present study, lentiviral‑mediated transfection and small interfering RNA (siRNA) were used to alter β-hCG expression in the ovarian cancer cell lines ES-2 and SKOV3, respectively...
July 14, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28713929/microrna-379-inhibits-metastasis-and-epithelial-mesenchymal-transition-via-targeting-fak-akt-signaling-in-gastric-cancer
#13
Meizhong Xu, Shui Qin, Fan Cao, Shi Ding, Mengnan Li
Accumulating evidence demonstrates that aberrant miRNAs contribute to gastric cancer (GC) development and progression. However, the roles of various miRNAs in GC remain to be determined. In the present study, we confirmed that a reduced miR-379 expression was present in GC tissues and cell lines. Our clinical analysis revealed that the downregulated miR-379 expression was significantly correlated with poor prognostic features including lymph node metastasis and advanced TNM stage. Moreover, we confirmed that miR-379 was a novel independent prognostic marker for predicting 5-year survival of GC patients...
July 12, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28713928/upregulation-of-wnt-signaling-under-hypoxia-promotes-lung-cancer-progression
#14
Chun-Fu Hong, Wei-You Chen, Cheng-Wen Wu
The hypoxic tumor microenvironment induces epithelial-mesenchymal transition (EMT) in tumor cells and increases tumor cell malignancy. Previous studies indicated that malfunction of Wnt signaling is observed in some lung cancer patients. Athough crosstalk between hypoxia and Wnt signaling in tumor cells has recently been revealed, the detailed underlying mechanisms have not been well defined. In the present study, we demonstrated that hypoxia in lung adenocarcinoma cells can enhance Wnt signaling activity by stabilizing β-catenin and altering its localization into the nucleus...
July 12, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28712972/arenobufagin-inhibits-prostate-cancer-epithelial-mesenchymal-transition-and-metastasis-by-down-regulating-%C3%AE-catenin
#15
Liping Chen, Weiqian Mai, Minfeng Chen, Jianyang Hu, Zhenjian Zhuo, Xueping Lei, Lijuan Deng, Junshan Liu, Nan Yao, Maohua Huang, Yinghui Peng, Wencai Ye, Dongmei Zhang
Epithelial-mesenchymal transition (EMT) plays an important role in prostate cancer (PCa) metastasis; thus, developing EMT inhibitors may be a feasible treatment for metastatic PCa. Here, we discovered that arenobufagin and four other bufadienolides suppressed PC3 cell EMT. These compounds modulated EMT marker expression with elevating E-cadherin and reducing ZEB1, vimentin and slug expression, and attenuated the migration and invasion of PC3 cells. Among these five compounds, arenobufagin exhibited the most potent activity...
July 13, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28711919/silencing-igfbp-2-decreases-pancreatic-cancer-metastasis-and-enhances-chemotherapeutic-sensitivity
#16
Huan Liu, Le Li, Hua Chen, Rui Kong, Shangha Pan, Jisheng Hu, Yongwei Wang, Yilong Li, Bei Sun
Pancreatic cancer has remained one of the most devastating and lethal malignancies characterized by local invasion, distant metastasis and a high degree of chemoresistance. Insulin-like growth factor binding protein 2 (IGFBP-2) is a member of the IGFBP family of proteins, and it is highly expressed in pancreatic cancer patients' serum and tumor tissues. IGFBP-2 also mediates tumor cell growth, invasion and resistance, while the mechanisms remain unclear. In this study, we sought to determine the impact of IGFBP-2 expression on pancreatic cancer tumorigenesis and metastasis in vitro and in vivo...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28711911/human-steroid-sulfatase-induces-wnt-%C3%AE-catenin-signaling-and-epithelial-mesenchymal-transition-by-upregulating-twist1-and-hif-1%C3%AE-in-human-prostate-and-cervical-cancer-cells
#17
Sangyun Shin, Hee-Jung Im, Yeo-Jung Kwon, Dong-Jin Ye, Hyoung-Seok Baek, Donghak Kim, Hyung-Kyoon Choi, Young-Jin Chun
Steroid sulfatase (STS) catalyzes the hydrolysis of estrone sulfate and dehydroepiandrosterone sulfate (DHEAS) to their unconjugated biologically active forms. Although STS is considered a therapeutic target for estrogen-dependent diseases, the cellular functions of STS remain unclear. We found that STS induces Wnt/β-catenin s Delete ignaling in PC-3 and HeLa cells. STS increases levels of β-catenin, phospho-β-catenin, and phospho-GSK3β. Enhanced translocation of β-catenin to the nucleus by STS might activate transcription of target genes such as cyclin D1, c-myc, and MMP-7...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28708313/human-biliverdin-reductase-regulates-the-molecular-mechanism-underlying-cancer-development
#18
Min Zhang, Wei Xin, Zhi Yi, Yue Li, Ying Liu, Hongyue Zhang, He Chen, Xinxin Chen, Shujie Tan, Daling Zhu
Human biliverdin reductase (hBVR), is an enzyme, that converts biliverdin to bilirubin, and has been implicated in epithelial-mesenchymal transition?EMT? in breast cancer. However, few studies have investigated the role of hBVR in cell apoptosis in other cancers. Therefore, the aim of this study was to investigate the effects of hBVR in several lines of cancer cells. The results of this study showed that hBVR expression was up-regulated in breast, lung, and liver cancers, but not ovarian cancer. Moreover, hBVR inhibition by small interfering RNA (si-hBVR) attenuated cell survival and increased caspase-3 protein expression, which was mediated by the ERK1/2 signaling pathway in relative cancer cells...
July 14, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28708138/blocking-endothelin-1-receptor-%C3%AE-catenin-circuit-sensitizes-to-chemotherapy-in-colorectal-cancer
#19
Roberta Cianfrocca, Laura Rosanò, Piera Tocci, Rosanna Sestito, Valentina Caprara, Valeriana Di Castro, Ruggero De Maria, Anna Bagnato
The limited clinical response to conventional chemotherapeutics observed in colorectal cancer (CRC) may be related to the connections between the hyperactivated β-catenin signaling and other pathways in CRC stem-like cells (CRC-SC). Here, we show the mechanistic link between the endothelin-1 (ET-1)/ET-1 receptor (ET-1R) signaling and β-catenin pathway through the specific interaction with the signal transducer β-arrestin1 (β-arr1), which initiates signaling cascades as part of the signaling complex. Using a panel of patient-derived CRC-SC, we show that these cells secrete ET-1 and express ETAR and β-arr1, and that the activation of ETAR/β-arr1 axis promotes the cross-talk with β-catenin signaling to sustain stemness, epithelial-to-mesenchymal transition (EMT) phenotype and response to chemotherapy...
July 14, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28706161/the-molecular-mechanisms-of-chemoresistance-in-cancers
#20
REVIEW
Hua-Chuan Zheng
Overcoming intrinsic and acquired drug resistance is a major challenge in treating cancer patients because chemoresistance causes recurrence, cancer dissemination and death. This review summarizes numerous molecular aspects of multi-resistance, including transporter pumps, oncogenes (EGFR, PI3K/Akt, Erk and NF-κB), tumor suppressor gene (p53), mitochondrial alteration, DNA repair, autophagy, epithelial-mesenchymal transition (EMT), cancer stemness, and exosome. The chemoresistance-related proteins are localized to extracellular ligand, membrane receptor, cytosolic signal messenger, and nuclear transcription factors for various events, including proliferation, apoptosis, EMT, autophagy and exosome...
July 6, 2017: Oncotarget
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