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https://www.readbyqxmd.com/read/28803777/paraoxonase-2-facilitates-pancreatic-cancer-growth-and-metastasis-by-stimulating-glut1-mediated-glucose-transport
#1
Arvindhan Nagarajan, Shaillay Kumar Dogra, Lisha Sun, Neeru Gandotra, Thuy Ho, Guoping Cai, Gary Cline, Priti Kumar, Robert A Cowles, Narendra Wajapeyee
Metabolic deregulation is a hallmark of human cancers, and the glycolytic and glutamine metabolism pathways were shown to be deregulated in pancreatic ductal adenocarcinoma (PDAC). To identify new metabolic regulators of PDAC tumor growth and metastasis, we systematically knocked down metabolic genes that were overexpressed in human PDAC tumor samples using short hairpin RNAs. We found that p53 transcriptionally represses paraoxonase 2 (PON2), which regulates GLUT1-mediated glucose transport via stomatin. The loss of PON2 initiates the cellular starvation response and activates AMP-activated protein kinase (AMPK)...
August 17, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28794639/kiaa1522-overexpression-promotes-tumorigenicity-and-metastasis-of-esophageal-cancer-cells-through-potentiating-the-erk-activity
#2
Zhi-Hui Xie, Jing Yu, Li Shang, Yi-Qing Zhu, Jia-Jie Hao, Yan Cai, Xin Xu, Yu Zhang, Ming-Rong Wang
Esophageal squamous cell carcinoma (ESCC) is a highly malignant tumor associated with a poor prognosis, and the molecular mechanisms underlying its formation and progression remain poorly understood. KIAA1522 is upregulated in various tumor tissues, but its function is unknown. Alterations in KIAA1522 expression and its implication in ESCC are currently unclear. In this study, an immunohistochemical analysis of ESCC tissues showed that KIAA1522 was highly expressed in 46% (157/342) of ESCC specimens and that its expression was inversely correlated with the degree of differentiation (P=0...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28792442/complex-determinants-of-epithelial-mesenchymal-phenotypic-plasticity-in-ovarian-cancer
#3
REVIEW
Yuliya Klymenko, Oleg Kim, M Sharon Stack
Unlike most epithelial malignancies which metastasize hematogenously, metastasis of epithelial ovarian cancer (EOC) occurs primarily via transcoelomic dissemination, characterized by exfoliation of cells from the primary tumor, avoidance of detachment-induced cell death (anoikis), movement throughout the peritoneal cavity as individual cells and multi-cellular aggregates (MCAs), adhesion to and disruption of the mesothelial lining of the peritoneum, and submesothelial matrix anchoring and proliferation to generate widely disseminated metastases...
August 9, 2017: Cancers
https://www.readbyqxmd.com/read/28775239/reversion-of-epithelial-mesenchymal-transition-by-a-novel-agent-dz-50-via-igf-binding-protein-3-in-prostate-cancer-cells
#4
Zheng Cao, Shahriar Koochekpour, Stephen E Strup, Natasha Kyprianou
Dysregulation of transforming growth factor-β1 (TGF-β1) and insulin-like growth factor (IGF) axis has been linked to reactive stroma dynamics in prostate cancer progression. IGF binding protein-3 (IGFBP3) induction is initiated by stroma remodeling and could represent a potential therapeutic target for prostate cancer. In previous studies a lead quinazoline-based Doxazosin® derivative, DZ-50, impaired prostate tumor growth by targeting proteins involved in focal adhesion, anoikis resistance and epithelial-mesenchymal-transition (EMT)...
July 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28767412/the-prognostic-value-of-over-expressed-trkb-in-solid-tumors-a-systematic-review-and-meta-analysis
#5
Chunze Zhang, Xiaoting Li, Dan Gao, Haihua Ruan, Zhenzhen Lin, Xiaobo Li, Guang Liu, Zhicheng Ma, Xichuan Li
It is reported recently Tropomyosin-related receptor Kinase B (TrkB) plays key roles in the anoikis resistance during the processes of tumorigenesis and metastasis. However, its prognostic significance for clinical patients remains inconclusive. In order to establish a correct and practicable link between increased TrkB and prognostication of human solid tumors, a meta-analysis was performed in this article. A systematic literature research in the electronic databases PubMed, Embase and Web of Science was performed to identify eligible studies...
July 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28755475/prostate-epithelium-basement-membrane-and-prostate-cell-biology-20-years
#6
Hernandes F Carvalho, Sebastião Roberto Taboga, Sérgio Luis Felisbino, Manoel F Biancardi
The basement membrane (BM) confines the epithelia and is an apparent barrier to metastasis. Progression to malignancy is associated with cancer cell's ability to breakdown the BM and to invade the adjacent stroma (Duffy 1992, Lochter et al., 1999). Invasion depends not only on their capacity to degrade BM components but also to survive the loss of cell-cell and cell-ECM adhesion, surpassing anoikis. Enhanced proteolysis of the cancer cell microenvironment is due to a repertoire of metalloproteinases (MMP) in disbalance with their endogenous inhibitors, such as the TIMPs, RECK and Kiss, as well as an increased in proteolytical enzymes, such as uPA (and other serine proteases) and ADAMs, capable of activating MMPs (Johnsen et al...
July 29, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28752076/molecular-machineries-of-ph-dysregulation-in-tumor-microenvironment-potential-targets-for-cancer-therapy
#7
REVIEW
Mohammad Reza Asgharzadeh, Jaleh Barar, Mohammad M Pourseif, Morteza Eskandani, Mojtaba Jafari Niya, Mohammad Reza Mashayekhi, Yadollah Omidi
Introduction: Cancer is an intricate disorder/dysfunction of cells that can be defined as a genetic heterogeneity in human disease. Therefore, it is characterized by several adaptive complex hallmarks. Among them, the pH dysregulation appears as a symbol of aberrant functions within the tumor microenvironment (TME). In comparison with normal tissues, in the solid tumors, we face with an irregular acidification and alkalinization of the extracellular and intracellular fluids. Methods: In this study, we comprehensively discussed the most recent reports on the hallmarks of solid tumors to provide deep insights upon the molecular machineries involved in the pH dysregulation of solid tumors and their impacts on the initiation and progression of cancer...
2017: BioImpacts: BI
https://www.readbyqxmd.com/read/28749463/cancer-cell-resistance-to-anoikis-muc1-glycosylation-comes-to-play
#8
Lu-Gang Yu
No abstract text is available yet for this article.
July 27, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28743280/exosomes-derived-from-gemcitabine-resistant-cells-transfer-malignant-phenotypic-traits-via-delivery-of-mirna-222-3p
#9
Feng Wei, Chengyuan Ma, Tong Zhou, Xuechao Dong, Qinghua Luo, Li Geng, Lijuan Ding, Yandong Zhang, Li Zhang, Nan Li, Yang Li, Yan Liu
BACKGROUND: Although gemcitabine-based chemotherapy has been established as a core multimodal therapy for non-small cell lung cancer (NSCLC) treatment, its clinical efficacy remains limited by the development of acquired resistance following tumor metastasis and relapse. In this study, we investigated how gemcitabine-resistant (GR) cells contribute to the development of NSCLC tumor malignancy via exosome-mediated transfer of microRNAs. METHODS: We first studied the mechanism of exosome internalization via PKH-67 staining and an immunofluorescence assay, then confirmed our finding by transmission electron microscopy and western blot analysis...
July 25, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28725490/muc1-o-glycosylation-contributes-to-anoikis-resistance-in-epithelial-cancer-cells
#10
Tushar Piyush, Jonathan M Rhodes, Lu-Gang Yu
Anoikis is a fundamental cellular process for maintaining tissue homeostasis. Resistance to anoikis is a hallmark of oncogenic epithelial-mesenchymal transition and is a pre-requisite for metastasis. Previous studies have revealed that the heavily glycosylated mucin protein MUC1, which is overexpressed in all types of epithelial cancer cells, prevents anoikis initiation in response to loss of adhesion. This effect of MUC1 is largely attributed to its extracellular domain that provides cell surface anoikis-initiating molecules with a 'homing' microenvironment...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28718402/metabolism-during-ecm-detachment-achilles-heel-of-cancer-cells
#11
REVIEW
Joshua A Mason, Kimberly R Hagel, Mark A Hawk, Zachary T Schafer
Integrin-mediated attachment to the extracellular matrix (ECM) is required to combat the induction of programmed cell death in a variety of distinct cell types. If cells fail to maintain proper ECM attachment, they become subject to elimination via an apoptotic cell death program known as anoikis. However, anoikis inhibition is not sufficient to promote the long-term survival of ECM-detached cells. Several recent studies have unveiled the profound (anoikis-independent) impact of cell metabolism on the viability of ECM-detached cells...
July 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28700115/lkb1-pro-oncogenic-activity-triggers-cell-survival-in-circulating-tumor-cells
#12
Elisabeth Katharina Trapp, Leonie Majunke, Beate Zill, Harald Sommer, Ulrich Andergassen, Julian Koch, Nadia Harbeck, Sven Mahner, Thomas Wolfram Paul Friedl, Wolfgang Janni, Brigitte Rack, Marianna Alunni-Fabbroni
During intravasation, circulating tumor cells (CTCs) detach from the epithelium of origin and begin the Epithelial-to Mesenchymal-Transition (EMT) process, where they lose epithelial features and pass through the endothelium to enter circulation. Although detachment from the extracellular matrix is a strong source of metabolic stress, which induces anoikis, CTCs can survive. Recently, the tumor suppressor liver kinase B1 (LKB1) has gained attention for its role as a proto-oncogene in restoring the correct ATP/AMP ratio during metabolic stress...
July 12, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28681073/%C3%AE-catenin-acts-as-a-tumor-suppressor-through-context-dependent-mechanisms-in-colorectal-cancer
#13
Jutta Maria Nagel, Harald Lahm, Andrea Ofner, Burkhard Göke, Frank Thomas Kolligs
PURPOSE: γ-Catenin is a protein closely related to β-catenin. While the overexpression of β-catenin has been linked with impaired prognosis and survival in various malignancies, both oncogenic and tumor suppressor functions have been described for γ-catenin. Thus, its role in cancer remains controversial. In this study, we examined the impact of γ-catenin expression on the malignant potential of colorectal cancer cells. METHODS: γ-Catenin was knocked down by short interfering RNA in the γ-catenin-proficient DLD-1 cell line and stably overexpressed in the γ-catenin-deficient cell line RKO...
July 6, 2017: International Journal of Colorectal Disease
https://www.readbyqxmd.com/read/28679861/enhanced-chemosensitization-of-anoikis-resistant-melanoma-cells-through-syndecan-2-upregulation-upon-anchorage-independency
#14
TingTing Tseng, WuChing Uen, JenChih Tseng, ShaoChen Lee
Syndecan family proteins are heparan sulfate proteoglycans, which involved in various cellular activities and associating with metastatic potential and chemosensitivity of tumor cells. Melanoma is one of malignant tumors with poor prognosis upon metastasis. Previously, we had shown that melanoma cells remained survived under cell detachment, which was similar to the initial steps of tumor metastasis. Downregulation of syndecan-1 and upregulation of syndecan-2 in melanoma A375 cells were observed by different suspension conditions...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28667075/axl-driven-emt-state-as-a-targetable-conduit-in-cancer
#15
REVIEW
Jane Antony, Ruby Yun-Ju Huang
The receptor tyrosine kinase (RTK) AXL has been intrinsically linked to epithelial-mesenchymal transition (EMT) and promoting cell survival, anoikis resistance, invasion, and metastasis in several cancers. AXL signaling has been shown to directly affect the mesenchymal state and confer it with aggressive phenotype and drug resistance. Recently, the EMT gradient has also been shown to rewire the kinase signaling nodes that facilitate AXL-RTK cross-talk, protracted signaling, converging on ERK, and PI3K axes...
June 30, 2017: Cancer Research
https://www.readbyqxmd.com/read/28653224/acquisition-of-anoikis-resistance-promotes-alterations-in-the-ras-erk-and-pi3k-akt-signaling-pathways-and-matrix-remodeling-in-endothelial-cells
#16
Ana Paula de Sousa Mesquita, Silvana de Araújo Lopes, Paulo Castanho A Pernambuco Filho, Helena B Nader, Carla Cristina Lopes
Anoikis is a programmed cell death induced upon cell detachment from extracellular matrix. Anoikis resistance is a critical mechanism in tumor metastasis. Cancer cells deregulate and adapt their metabolism to survive in the absence of adhesion, spreading metastases to distant organs. These adaptations include abnormal regulation of growth factor receptors activating prosurvival signaling pathways, such as the Ras/ERK and PI3K/Akt pathways, and extracellular matrix remodeling, leading to metastasis by an increase of invasiveness and inhibiting anoikis...
June 26, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28646172/dacomitinib-a-pan-inhibitor-of-erbb-receptors-suppresses-growth-and-invasive-capacity-of-chemoresistant-ovarian-carcinoma-cells
#17
Majid Momeny, Ghazaleh Zarrinrad, Farima Moghaddaskho, Arash Poursheikhani, Ghazaleh Sankanian, Azam Zaghal, Shahab Mirshahvaladi, Fatemeh Esmaeili, Haniyeh Eyvani, Farinaz Barghi, Zahra Sabourinejad, Zivar Alishahi, Hassan Yousefi, Reza Ghasemi, Leila Dardaei, Davood Bashash, Bahram Chahardouli, Ahmad R Dehpour, Javad Tavakkoly-Bazzaz, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy worldwide. Development of chemoresistance and peritoneal dissemination of EOC cells are the major reasons for low survival rate. Targeting signal transduction pathways which promote therapy resistance and metastatic dissemination is the key to successful treatment. Members of the ErbB family of receptors are over-expressed in EOC and play key roles in chemoresistance and invasiveness. Despite this, single-targeted ErbB inhibitors have demonstrated limited activity in chemoresistant EOC...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28641978/angptl4-t266m-variant-is-associated-with-reduced-cancer-invasiveness
#18
Zhen Wei Tan, Ziqiang Teo, Carol Tan, Chee Chong Choo, Wei Sheng Loo, Yiyang Song, Zhi Yang Tam, Sean Pin Ng, Hong Zheng Koh, Yi Siang Ng, Susana Geifman Shochat, Yin Hoe Yau, Pengcheng Zhu, Nguan Soon Tan
Angiopoietin-like 4 (ANGPTL4) is a secretory protein that can be cleaved to form an N-terminal and a C-terminal protein. Studies performed thus far have linked ANGPTL4 to several cancer-related and metabolic processes. Notably, several point mutations in the C-terminal ANGPTL4 (cANGPTL4) have been reported, although no studies have been performed that ascribed these mutations to cancer-related and metabolic processes. In this study, we compared the characteristics of tumors with and without wild-type (wt) cANGPTL4 and tumors with cANGPTL4 bearing the T266M mutation (T266M cANGPTL4)...
June 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28637020/autophagy-related-genes-are-induced-by-histone-deacetylase-inhibitor-suberoylanilide-hydroxamic-acid-via-the-activation-of-cathepsin-b-in-human-breast-cancer-cells
#19
Han Han, Jing Li, Xiuyan Feng, Hui Zhou, Shanchun Guo, Weiqiang Zhou
Autophagy is involved in modulating tumor cell motility and invasion, resistance to epithelial-to-mesenchymal transition, anoikis, and escape from immune surveillance. We have previous shown that SAHA is capable to induce several apoptosis and autophagy-related gene expression in breast cancers. However, the exact mechanisms of autophagy activation in this context have not been fully identified. Our results showed that the expression and the activity of Cathepsin B (CTSB), one of the major lysosomal cysteine proteases, were significantly increased in MDA-MB- 231 and MCF-7 cells upon SAHA treatment...
June 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28604746/oncogenic-k-ras-upregulates-itga6-expression-via-fosl1-to-induce-anoikis-resistance-and-synergizes-with-%C3%AE-v-class-integrins-to-promote-emt
#20
K Zhang, S-M Myllymäki, P Gao, R Devarajan, V Kytölä, M Nykter, G-H Wei, A Manninen
In many cancer types, integrin-mediated signaling regulates proliferation, survival and invasion of tumorigenic cells. However, it is still unclear how integrins crosstalk with oncogenes to regulate tumorigenesis and metastasis. Here we show that oncogenic K-Ras(V12) upregulates α6-integrin expression in Madin-Darby canine kidney (MDCK) cells via activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK)/Fos-related antigen 1-signaling cascade. Activated α6-integrins promoted metastatic capacity and anoikis resistance, and led to perturbed growth of MDCK cysts...
June 12, 2017: Oncogene
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