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Epithelial mesenchymal transformation

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https://www.readbyqxmd.com/read/28213007/effect-of-dasatinib-on-emt-mediated-mechanism-of-resistance-against-egfr-inhibitors-in-lung-cancer-cells
#1
Yuichi Sesumi, Kenichi Suda, Hiroshi Mizuuchi, Yoshihisa Kobayashi, Katsuaki Sato, Masato Chiba, Masaki Shimoji, Kenji Tomizawa, Toshiki Takemoto, Tetsuya Mitsudomi
OBJECTIVE: The epithelial to mesenchymal transition (EMT) is associated with acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in certain non-small cell lung cancers that harbor EGFR mutations. Because no currently available drugs specifically kill cancer cells via EMT, novel treatment strategies that overcome or prevent EMT are needed. A recent report suggested that dasatinib (an ABL/Src kinase inhibitor) inhibits EMT induced by transforming growth factor (TGF)-beta in lung cancer cells (Wilson et al...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28209158/gene-regulatory-network-underlying-the-immortalization-of-epithelial-cells
#2
Luis Fernando Méndez-López, Jose Davila-Velderrain, Elisa Domínguez-Hüttinger, Christian Enríquez-Olguín, Juan Carlos Martínez-García, Elena R Alvarez-Buylla
BACKGROUND: Tumorigenic transformation of human epithelial cells in vitro has been described experimentally as the potential result of spontaneous immortalization. This process is characterized by a series of cell-state transitions, in which normal epithelial cells acquire first a senescent state which is later surpassed to attain a mesenchymal stem-like phenotype with a potentially tumorigenic behavior. In this paper we aim to provide a system-level mechanistic explanation to the emergence of these cell types, and to the time-ordered transition patterns that are common to neoplasias of epithelial origin...
February 16, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28202676/harnessing-the-bmp-signaling-pathway-to-control-the-formation-of-cancer-stem-cells-by-effects-on-epithelial-to-mesenchymal-transition
#3
REVIEW
Ashish Bosukonda, William D Carlson
Cancer stem cells (CSCs) persist in tumors as a distinct population and may be causative in metastasis and relapse. CSC-rich tumors are associated with higher rates of metastasis and poor patient prognosis. Targeting CSCs therapeutically is challenging, since they seem to be resistant to standard chemotherapy. We have shown that a novel peptide agonist of bone morphogenetic protein (BMP) signaling, P123, is capable of inhibiting the growth of primary tumor cells by interacting with type I receptors selectively [activin receptor-like kinase 2 (ALK2) and ALK3, but not ALK6] and type II BMP receptors, activating SMAD 1/5/8 signaling and controlling the cell cycle pathway...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28191776/clinical-grade-isolated-human-kidney-perivascular-stromal-cells-as-an-organotypic-cell-source-for-kidney-regenerative-medicine
#4
Daniëlle G Leuning, Marlies E J Reinders, Joan Li, Anna J Peired, Ellen Lievers, Hetty C de Boer, Willem E Fibbe, Paola Romagnani, Cees van Kooten, Melissa H Little, Marten A Engelse, Ton J Rabelink
Mesenchymal stromal cells (MSCs) are immunomodulatory and tissue homeostatic cells that have shown beneficial effects in kidney diseases and transplantation. Perivascular stromal cells (PSCs) identified within several different organs share characteristics of bone marrow-derived MSCs (BM-MSCs). These PSCs may also possess tissue-specific properties and play a role in local tissue homeostasis. We hypothesized that human kidney-derived PSCs (hkPSCs) would elicit improved kidney repair in comparison with BM-MSCs...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28188683/functional-kras-mutations-and-a-potential-role-for-pi3k-akt-activation-in-wilms-tumors
#5
Dina Polosukhina, Harold D Love, Hernan Correa, Zengliu Su, Kimberly B Dahlman, William Pao, Harold L Moses, Carlos L Arteaga, Harold N Lovvorn, Roy Zent, Peter E Clark
Wilms tumor (WT) is the most common renal neoplasm of childhood and affects 1 in 10,000 children aged less than 15 years. These embryonal tumors are thought to arise from primitive nephrogenic rests that derive from the metanephric mesenchyme during kidney development and are characterized partly by increased Wnt/β-catenin signaling. We previously showed that coordinate activation of Ras and β-catenin accelerates the growth and metastatic progression of a murine WT model. Here, we show that activating KRAS mutations can be found in human WT...
February 11, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28185461/-epithelial-mesenchymal-transition-in-tumor-tissue-and-its-role-for-metastatic-spread-of-cancer
#6
V M Matějka, J Fínek, M Králíčková
BACKGROUND: Metastasis, recurrence, and resistance to chemotherapy are leading causes of the majority of cancer-related mortality worldwide. The process of metastasis can be artificially divided into a series of sequential, highly organized, and organ-specific steps. The underlying mechanisms are still poorly understood, but are believed to be mediated by epithelial-mesenchymal transition (EMT). First described in embryogenesis, EMT is a cellular reprogramming process in which epithelial cells acquire a mesenchymal phenotype...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28182993/de-novo-emergence-of-mesenchymal-stem-like-cd105-cancer-cells-by-cytotoxic-agents-in-human-hepatocellular-carcinoma
#7
Yoshimoto Nomura, Taro Yamashita, Naoki Oishi, Kouki Nio, Takehiro Hayashi, Mariko Yoshida, Tomoyuki Hayashi, Tomomi Hashiba, Yasuhiro Asahina, Hikari Okada, Hajime Sunagozaka, Hajime Takatori, Masao Honda, Shuichi Kaneko
BACKGROUND: Cancer stem cells (CSCs) are considered a pivotal target for the eradication of hepatocellular carcinoma (HCC). Recently, we reported that the CSC markers epithelial cell adhesion molecule (EpCAM) and CD90 are expressed independently in primary HCCs and cell lines, and CD90(+) cells share features of metastatic vascular endothelial cells and express the vascular endothelial marker CD105, a co-receptor of transforming growth factor-beta. METHODS: The EpCAM(+) cell lines HuH1 and HuH7 were treated with 5-fluorouracil (5-FU) or epirubicin in vitro...
February 6, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28182573/amplified-canonical-transforming-growth-factor-%C3%AE-signalling-via-heat-shock-protein-90-in-pulmonary-fibrosis
#8
Zaneta Sibinska, Xia Tian, Martina Korfei, Baktybek Kojonazarov, Janina Susanne Kolb, Walter Klepetko, Djuro Kosanovic, Malgorzata Wygrecka, Hossein Ardeschir Ghofrani, Norbert Weissmann, Friedrich Grimminger, Werner Seeger, Andreas Guenther, Ralph T Schermuly
Interstitial lung fibroblast activation coupled with extracellular matrix production is a pathological signature of idiopathic pulmonary fibrosis (IPF), and is governed by transforming growth factor (TGF)-β/Smad signalling. We sought to define the role of heat shock protein (HSP)90 in profibrotic responses in IPF and to determine the therapeutic effects of HSP90 inhibition in a murine model of pulmonary fibrosis.We investigated the effects of HSP90 inhibition in vitro by applying 17-AAG (17-allylamino-17-demethoxygeldanamycin) to lung fibroblasts and A549 cells and in vivo by administering 17-DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin) to mice with bleomycin-induced pulmonary fibrosis...
December 19, 2016: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28178615/long-non-coding-rna-tug1-promotes-cell-proliferation-and-metastasis-by-negatively-regulating-mir-300-in-gallbladder-carcinoma
#9
Fei Ma, Shou-Hua Wang, Qiang Cai, Long-Yang Jin, Di Zhou, Jun Ding, Zhi-Wei Quan
BACKGROUND: As we all know, long non-coding RNAs (lncRNAs) have been reported to play vital roles in various human cancers. In this study, we aimed to explore the role of lncRNA TUG1 in gallbladder carcinoma (GBC) development. METHODS: Total RNA was extracted from the tissues of thirty GBC patients, four GBC cell lines. We detected the expression levels of TUG1 using quantitative real-time PCR. We performed CCK8, colony formation, transwell invasion and apoptosis assays to study the effects of TUG1 on GBC cell proliferation and invasion...
February 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28176852/a-critical-role-of-platelet-tgf-%C3%AE-release-in-podoplanin-mediated-tumour-invasion-and-metastasis
#10
Ai Takemoto, Mina Okitaka, Satoshi Takagi, Miho Takami, Shigeo Sato, Makoto Nishio, Sakae Okumura, Naoya Fujita
The tumour microenvironment is critical for various characteristics of tumour malignancies. Platelets, as part of the tumour microenvironment, are associated with metastasis formation via increasing the rate of tumour embolus formation in microvasculature. However, the mechanisms underlying the ability of tumour cells to acquire invasiveness and extravasate into target organs at the site of embolization remain unclear. In this study, we reported that platelet aggregation-inducing factor podoplanin expressed on tumour cell surfaces were found to not only promote the formation of tumour-platelet aggregates via interaction with platelets, but also induced the epithelial-mesenchymal transition (EMT) of tumour cells by enhancing transforming growth factor-β (TGF-β) release from platelets...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28176240/the-crosstalk-between-long-non-coding-rnas-and-pi3k-in-cancer
#11
REVIEW
Leonidas Benetatos, Evangelos Voulgaris, Georgios Vartholomatos
Long non-coding RNAs (lncRNAs) are able to positively or negatively regulate other genes expression in cis or in trans. Their effect can be achieved through RNA-protein, RNA-DNA, or RNA-RNA interactions. They can recruit transcription factors and act as scaffolds or guides for chromatin-modifying enzymes. PI3K kinases transform external stimuli to intracellular signals regulating cell growth, differentiation, proliferation, survival, intracellular trafficking, cytoskeletal changes, cell migration and motility, and metabolism...
March 2017: Medical Oncology
https://www.readbyqxmd.com/read/28174483/dual-effect-of-wisp-1-in-diverse-pathological-processes
#12
Mengmeng Feng, Shuqin Jia
Wnt-1 inducible signaling pathway-1 (WISP-1), also known as CCN-4, belongs to the connective tissue growth factor (CTGF) family. WISP-1 is primarily expressed in embryonic stem cells and is involved in adult organ development. WISP-1 participates in many cellular processes, including proliferation, differentiation, apoptosis and adhesion. In addition, WISP-1 plays an important role in diverse pathophysiological processes, such as embryonic development, inflammation, injury repairs and cancers. Recent studies showed that WISP-1 was highly correlated with tumor progression and malignant transformation, whereas it played an oncogenic role in colorectal cancer, cholangiocarcinoma, hepatocellular carcinoma and breast cancer...
December 2016: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/28169915/vaginal-estrogen-a-dual-edged-sword-in-postoperative-healing-of-the-vaginal-wall
#13
Christopher M Ripperda, Pedro Antonio Maldonado, Jesus F Acevedo, Patrick W Keller, Yucel Akgul, John M Shelton, Ruth Ann Word
OBJECTIVE: Reconstructive surgery for pelvic organ prolapse is plagued with high failure rates possibly due to impaired healing or regeneration of the vaginal wall. Here, we tested the hypothesis that postoperative administration of local estrogen, direct injection of mesenchymal stem cells (MSCs), or both lead to improved wound healing of the injured vagina in a menopausal rat model. METHODS: Ovariectomized rats underwent surgical injury to the posterior vaginal wall and were randomized to treatment with placebo (n = 41), estrogen cream (n = 47), direct injection of MSCs (n = 39), or both (n = 43)...
February 6, 2017: Menopause: the Journal of the North American Menopause Society
https://www.readbyqxmd.com/read/28167863/biomechanical-cell-regulatory-networks-as-complex-adaptive-systems-in-relation-to-cancer
#14
REVIEW
Liviu Feller, Razia Abdool Gafaar Khammissa, Johan Lemmer
Physiological structure and function of cells are maintained by ongoing complex dynamic adaptive processes in the intracellular molecular pathways controlling the overall profile of gene expression, and by genes in cellular gene regulatory circuits. Cytogenetic mutations and non-genetic factors such as chronic inflammation or repetitive trauma, intrinsic mechanical stresses within extracellular matrix may induce redirection of gene regulatory circuits with abnormal reactivation of embryonic developmental programmes which can now drive cell transformation and cancer initiation, and later cancer progression and metastasis...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28167342/cellular-transformation-of-human-mammary-epithelial-cells-by-satb2
#15
Wei Yu, Yiming Ma, Augusto C Ochoa, Sharmila Shankar, Rakesh K Srivastava
Breast tumors are heterogeneous and carry a small population of progenitor cells that can produce various subtypes of breast cancer. SATB2 (special AT-rich binding protein-2) is a newly identified transcription factor and epigenetic regulator. It is highly expressed in embryonic stem cells, but not in adult tissues, and regulates pluripotency-maintaining factors. However, the molecular mechanisms by which SATB2 induces transformation of human mammary epithelial cells (HMECs) leading to malignant phenotype are unknown...
February 1, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28164090/met-roles-in-epithelial-mesenchymal-transition-and-cancer-stemness
#16
REVIEW
Hye-Min Jeon, Jeongwu Lee
In a number of cancers, deregulated MET pathway leads to aberrantly activated proliferative and invasive signaling programs that promote malignant transformation, cell motility and migration, angiogenesis, survival in hypoxia, and invasion. A better understanding of oncogenic MET signaling will help us to discover effective therapeutic approaches and to identify which tumors are likely to respond to MET-targeted cancer therapy. In this review, we will summarize the roles of MET signaling in cancer, with particular focus on epithelial-mesenchymal transition (EMT) and cancer stemness...
January 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28161638/6-phosphofructo-2-kinase-fructose-2-6-bisphosphatase-3-is-required-for-transforming-growth-factor-%C3%AE-1-enhanced-invasion-of-panc1-cells-in%C3%A2-vitro
#17
Abdullah Yalcin, Tugba H Solakoglu, Selahattin C Ozcan, Saime Guzel, Sabire Peker, Serap Celikler, Basak D Balaban, Elif Sevinc, Yunus Gurpinar, Jason A Chesney
Transforming growth factor β1 (TGFβ1) is a well-established inducer of the epithelial-mesenchymal transition (EMT) that is essential for the acquisition of malignant properties, such as invasion, in tumor cells. Although recent studies suggest that the EMT in tumor cells is associated with reprogramming of energy metabolism and TGFβ1 has been shown to stimulate glycolysis in multiple primary cell lines, little is known about TGFβ1's effect on glycolysis and glycolytic regulators in transformed cells. Given the known regulatory role of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase-3 (PFKFB3) in glycolysis and association of glycolytic activity with malignant features such as invasion, we sought to investigate whether TGFβ1 regulates PFKFB3 expression and if PFKFB3 is involved in the TGFβ1-mediated increase in the invasive ability of the Panc1 cell cline-a well-established model of TGFβ1-initiated EMT...
February 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28161507/transforming-growth-factor-%C3%AE-induced-plasticity-causes-a-migratory-stemness-phenotype-in-hepatocellular-carcinoma
#18
Andrea Malfettone, Jitka Soukupova, Esther Bertran, Eva Crosas-Molist, Raquel Lastra, Joan Fernando, Petra Koudelkova, Bhavna Rani, Ángels Fabra, Teresa Serrano, Emilio Ramos, Wolfgang Mikulits, Gianluigi Giannelli, Isabel Fabregat
As part of its potential pro-tumorigenic actions, Transforming Growth Factor-(TGF)-β induces epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) cells. Whether EMT induces changes in tumor cell plasticity has not been fully explored yet. Here, we analyze the effects of TGF-β on the EMT and stem-related properties of HCC cells and the potential correlation among those processes. The translational aim of the study was to propose a TGF-β/EMT/stem gene signature that would help in recognizing HCC patients as good candidates for anti-TGF-β therapy...
February 2, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28152139/bone-morphogenetic-protein-7-suppresses-tgf%C3%AE-2-induced-epithelial-mesenchymal-transition-in-the-lens-implications-for-cataract-prevention
#19
Daisy Y Shu, Magdalena C Wojciechowski, Frank J Lovicu
Purpose: Epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is a key pathologic mechanism underlying cataract. Two members of the transforming growth factor-β (TGFβ) superfamily, TGFβ and bone morphogenetic protein-7 (BMP-7) have functionally distinct roles in EMT. While TGFβ is a potent inducer of EMT, BMP-7 counteracts the fibrogenic activity of TGFβ. We examine the modulating effect of BMP-7 on TGFβ-induced EMT in LECs. Methods: Rat lens epithelial explants were treated exogenously with TGFβ2 alone or in combination with BMP-7 for up to 5 days...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28151486/star-pap-a-poly-a-polymerase-functions-as-a-tumor-suppressor-in-an-orthotopic-human-breast-cancer-model
#20
C Yu, Y Gong, H Zhou, M Wang, L Kong, J Liu, T An, H Zhu, Y Li
Star-PAP is a noncanonical poly(A) polymerase and required for the expression of a select set of mRNAs. However, the pathological role of Star-PAP in cancer largely remains unknown. In this study, we observed decreased expression of Star-PAP in breast cancer cell lines and tissues. Ectopic Star-PAP expression inhibited proliferation as well as colony-forming ability of breast cancer cells. In breast cancer patients, high levels of Star-PAP correlated with an improved prognosis. Moreover, by regulating the expression of BIK (BCL2-interacting killer), Star-PAP induced apoptosis of breast cancer cells through the mitochondrial pathway...
February 2, 2017: Cell Death & Disease
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