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Jessica Byerly, Gwyneth Halstead-Nussloch, Koichi Ito, Igor Katsyv, Hanna Y Irie
BACKGROUND: The protein kinase C (PKC) family comprises distinct classes of proteins, many of which are implicated in diverse cellular functions. Protein tyrosine kinase C theta isoform (PRKCQ)/PKCθ, a member of the novel PKC family, may have a distinct isoform-specific role in breast cancer. PKCθ is preferentially expressed in triple-negative breast cancer (TNBC) compared to other breast tumor subtypes. We hypothesized that PRKCQ/PKCθ critically regulates growth and survival of a subset of TNBC cells...
2016: Breast Cancer Research: BCR
Diana Braunholz, Mohammad Saki, Franziska Niehr, Merve Öztürk, Berta Borràs Puértolas, Robert Konschak, Volker Budach, Ingeborg Tinhofer
In solid tumours millions of cells are shed into the blood circulation each day. Only a subset of these circulating tumour cells (CTCs) survive, many of them presumable because of their potential to form multi-cellular clusters also named spheroids. Tumour cells within these spheroids are protected from anoikis, which allows them to metastasize to distant organs or re-seed at the primary site. We used spheroid cultures of head and neck squamous cell carcinoma (HNSCC) cell lines as a model for such CTC clusters for determining the role of the epidermal growth factor receptor (EGFR) in cluster formation ability and cell survival after detachment from the extra-cellular matrix...
2016: PloS One
Xiaolin Zhang, Hao Yu
The proliferation of hepatocellular carcinoma (HCC) cells is one of the leading causes of liver cancer mortality in humans. The inhibiting effects of matrine on HCC cell proliferation have been studied, but the mechanism of that inhibition has not been fully elucidated. Since, apoptosis plays an important role in HCC cell proliferation. We examined the apoptosis-inducing effect of matrine on tumor cells. Western blot analysis of p53, Bax, cleaved caspase-3 and myosin light chain kinase (MLCK) revealed that matrine induced tumor cell apoptosis by controlling anoikis...
2016: Iranian Journal of Pharmaceutical Research: IJPR
L Castagnoli, G C Ghedini, A Koschorke, T Triulzi, M Dugo, P Gasparini, P Casalini, A Palladini, M Iezzi, A Lamolinara, P L Lollini, P Nanni, C Chiodoni, E Tagliabue, S M Pupa
We have previously shown that the d16HER2 splice variant is linked to HER2-positive breast cancer (BC) tumorigenesis, progression and response to Trastuzumab. However, the mechanisms by which d16HER2 contributes to HER2-driven aggressiveness and targeted therapy susceptibility remain uncertain. Here, we report that the d16HER2-positive mammary tumor cell lines MI6 and MI7, derived from spontaneous lesions of d16HER2 transgenic (tg) mice and resembling the aggressive features of primary lesions, are enriched in the expression of Wnt, Notch and epithelial-mesenchymal transition pathways related genes compared with full-length wild-type (WT) HER2-positive cells (WTHER2_1 and WTHER2_2) derived from spontaneous tumors arising in WTHER2 tg mice...
September 19, 2016: Oncogene
Maricel C Gozo, Dongyu Jia, Paul-Joseph Aspuria, Dong-Joo Cheon, Naoyuki Miura, Ann E Walts, Beth Y Karlan, Sandra Orsulic
Osteosarcoma is a highly malignant tumor that contains a small subpopulation of tumor-propagating cells (also known as tumor-initiating cells) characterized by drug resistance and high metastatic potential. The molecular mechanism by which tumor-propagating cells promote tumor growth is poorly understood. Here, we report that the transcription factor forkhead box C2 (FOXC2) is frequently expressed in human osteosarcomas and is important in maintaining osteosarcoma cells in a stem-like state. In osteosarcoma cell lines, we show that anoikis conditions stimulate FOXC2 expression...
September 13, 2016: Oncotarget
Wei-Ching Chen, Hui-Ping Hsu, Chung-Yen Li, Ya-Ju Yang, Yu-Hsuan Hung, Chien-Yu Cho, Chih-Yang Wang, Tzu-Yang Weng, Ming-Derg Lai
Cancer stem cell (CSC) markers have been identified for CSC isolation and proposed as therapeutic targets in various types of cancers. CD90, one of the characterized markers in liver and gastric cancer, is shown to promote cancer formation. However, the underexpression level of CD90 in ovarian cancer cells and the evidence supporting the cellular mechanism have not been investigated. In the present study, we found that the DNA copy number of CD90 is correlated with mRNA expression in ovarian cancer tissue and the ovarian cancer patients with higher CD90 have good prognosis compared to the patients with lower CD90...
September 15, 2016: International Journal of Oncology
Fiorella Di Claudio, Cecilia Muglia, Paola Smaldini, María Lucía Orsini Delgado, Fernando Trejo, Raúl Grigera, Guillermo Docena
Intestinal epithelial cell culture is important for biological, functional and immunological studies. Since enterocytes have a short in vivo life span due to anoikis, we aimed to establish a novel and reproducible method to prolong the survival of mouse and human cells. Cells were isolated following a standard procedure, and cultured on ordered-cow's collagen membranes. A prolonged cell life span was achieved; cells covered the complete surface of bio-membranes and showed a classical enterocyte morphology with high expression of enzymes supporting the possibility of cryopreservation...
September 14, 2016: Journal of Cellular Physiology
Elisabetta Bigagli, Cristina Luceri, Daniele Guasti, Lorenzo Cinci
Cancer-secreted exosomes influence tumor microenvironment and support cancer growth and metastasis. MiR-210 is frequently up-regulated in colorectal cancer tissues and correlates with metastatic disease. We investigated whether exosomes are actively released by HCT-8 colon cancer cells, the role of exosomal miR-210 in the cross-talk between primary cancer cells and neighboring metastatic cells and its contribution in regulating epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET)...
August 11, 2016: Cancer Biology & Therapy
Jiao Zhang, Ling Guo, Xia Zhou, Fengyun Dong, Liqun Li, Zuowang Cheng, Yinghua Xu, Jiyong Liang, Qi Xie, Ju Liu
Angiogenesis is required for the growth and metastasis of solid tumors. The anti-malarial agent dihydroartemisinin (DHA) demonstrates potent anti-angiogenic activity, but the underlying molecular mechanisms are not yet fully understood. During the process of angiogenesis, endothelial cells migrating from existing capillaries may undergo programmed cell death after detaching from the extracellular matrix, a process that is defined as anchorage-dependent apoptosis or anoikis. In the present study, DHA-induced cell death was compared in human umbilical vein endothelial cells (HUVECs) cultured in suspension and attached to culture plates...
September 2016: Oncology Letters
Wun Hak Choo, Cho Hee Park, Shi Eun Jung, Byeonghak Moon, Huiyeon Ahn, Jung Seok Ryu, Keun-Soo Kim, Yong Hwa Lee, Il Je Yu, Seung Min Oh
To predict carcinogenic potential of AgNPs on the respiratory system, BEAS-2B cells (human bronchial epithelial cells) were chronically exposed to low- and non-cytotoxic dose (0.13 and 1.33μg/ml) of AgNPs for 4months (#40 passages). To assess malignant cell transformation of chronic exposure to AgNPs, several bioassays including anchorage independent agar colony formation, cell migration/invasion assay, and epithelial-mesenchymal transition (EMT) were performed in BEAS-2B cells. Chronic exposure to AgNPs showed a significant increase of anchorage independent agar colony formation and cell migration/invasion...
December 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
E E Mowers, M N Sharifi, K F Macleod
Autophagy is a highly conserved self-degradative process that has a key role in cellular stress responses and survival. Recent work has begun to explore the function of autophagy in cancer metastasis, which is of particular interest given the dearth of effective therapeutic options for metastatic disease. Autophagy is induced upon progression of various human cancers to metastasis and together with data from genetically engineered mice and experimental metastasis models, a role for autophagy at nearly every phase of the metastatic cascade has been identified...
September 5, 2016: Oncogene
Ru-Feng Wu, Chengxu Liao, Guosheng Fu, Heather N Hayenga, Kejia Yang, Zhenyi Ma, Zhe Liu, Lance S Terada
Tissue cells respond to changes in tensional forces with proliferation or death through the control of RhoA. However, the response coupling mechanisms that link force with RhoA activation are poorly understood. We found that tension applied to fibronectin-coated microbeads caused recruitment of all three isoforms of the Shc adapter (p66(Shc), p52(Shc), and p46(Shc)) to adhesion complexes. The Shc PTB domain was necessary and sufficient for this recruitment, and screening studies revealed direct interactions with the FERM domain of FAK that were required for Shc translocation to adhesion complexes...
August 29, 2016: Molecular and Cellular Biology
Peng Zhang, Lifeng Chen, Yarong Song, Xuechao Li, Yadong Sun, Yajun Xiao, Yifei Xing
UNLABELLED: Prostate cancer is one of the most common malignancies in adult males and metastasis is the leading cause of death cases without satisfactory treatment options. Anoikis-resistance and migration are crucial aspects for the metastasis of various human cancer cells including prostate cancer and L-thyroxin (T4) has been proved to play vital roles in tumor metastasis. The present study demonstrated that T4 promoted migration and depressed detachment-induced apoptosis in anoikis-resistant prostate cancer cells while tetraiodothyroacetic acid (tetrac), a competitive antagonist of T4 at integrin αvβ3, reversed T4 induced effects through diminishing expressions of XIAP, MMP-2, VEGF together with inhibited activity of MAPK/ERK pathway...
October 1, 2016: Experimental Cell Research
H M Tang, K T Kuay, P F Koh, M Asad, T Z Tan, V Y Chung, S C Lee, J P Thiery, Ry-J Huang
Epithelial-mesenchymal transition (EMT), a crucial mechanism in development, mediates aggressiveness during carcinoma progression and therapeutic refractoriness. The reversibility of EMT makes it an attractive strategy in designing novel therapeutic approaches. Therefore, drug discovery pipelines for EMT reversal are in need to discover emerging classes of compounds. Here, we outline a pre-clinical drug screening platform for EMT reversal that consists of three phases of drug discovery and validation. From the Phase 1 epithelial marker promoter induction (EpI) screen on a library consisting of compounds being approved by Food and Drug Administration (FDA), Vorinostat (SAHA), a histone deacetylase inhibitor (HDACi), is identified to exert EMT reversal effects by restoring the expression of an epithelial marker, E-cadherin...
2016: Cell Death Discovery
X F Lu, X F Xia, G Chen
OBJECTIVE: To investigate the role of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in the metastasis of colorectal cancer and underlying mechanisms. METHODS: A colorectal cancer LoVo cell line transfected with a lentivirus vector stably expressinga shRNA targeting PGC-1αwas established. Cell proliferation was detected by CCK8 array. Migration and invasion were determined by Transwell assay. The expressions of epithelial-mesenchymal transition (EMT) markers were examined by western blot analysis...
July 2016: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
Asha M Das, Michiel Bolkestein, Thom van der Klok, Charlotte M C Oude Ophuis, Cindy E Vermeulen, Joost A P Rens, Winand N M Dinjens, Peggy N Atmodimedjo, Cornelis Verhoef, Senada Koljenović, Ron Smits, Timo L M Ten Hagen, Alexander M M Eggermont
AIMS: Malignant melanoma is the most aggressive form of skin cancer, and metastatic dissemination to regional and visceral sites is responsible for the majority of melanoma-related mortalities. In a recent study by our group, we observed reduced expression of tissue inhibitor of metalloproteinase-3 (TIMP3) in the majority of stage III melanoma samples studied. TIMP3 has been reported as a tumour suppressor in several human malignancies, with reduced expression correlating with poor clinical outcome...
October 2016: European Journal of Cancer
Laura Casarrubios, María Concepción Matesanz, Sandra Sánchez-Salcedo, Daniel Arcos, María Vallet-Regí, María Teresa Portolés
HYPOTHESIS: Silicon substituted hydroxyapatites (SiHA) are highly crystalline bioceramics treated at high temperatures (about 1200°C) which have been approved for clinical use with spinal, orthopedic, periodontal, oral and craniomaxillofacial applications. The preparation of SiHA with lower temperature methods (about 700°C) provides nanocrystalline SiHA (nano-SiHA) with enhanced bioreactivity due to higher surface area and smaller crystal size. The aim of this study has been to know the nanocrystallinity effects on the response of both osteoblasts and osteoclasts (the two main cell types involved in bone remodelling) to silicon substituted hydroxyapatite...
November 15, 2016: Journal of Colloid and Interface Science
Aarti Sethuraman, Martin Brown, Tiffany N Seagroves, Zhao-Hui Wu, Lawrence M Pfeffer, Meiyun Fan
BACKGROUND: While aberrant activation of the chromatin-remodeling SWI/SNF complexes has been associated with cancer development and progression, the role of each subunit in tumor cells is poorly defined. This study is aimed to characterize the role of SMARCE1/BAF57 in regulating metastasis of breast cancer cells. METHODS: Genetic approaches and chemical inhibitors were used to manipulate the activities of SMARCE1 and its downstream targets in multiple breast cancer cell lines...
2016: Breast Cancer Research: BCR
Gabriel Gallo-Oller, Arabel Vollmann-Zwerenz, Bárbara Meléndez, Juan A Rey, Peter Hau, Javier Dotor, Javier S Castresana
Glioblastoma (GBM) is the most prevalent malignant primary brain tumor, accounting for 60-70% of all gliomas. Current median patient survival time is 14-16 months after diagnosis. Numerous efforts in therapy have not significantly altered the nearly uniform lethality of this malignancy. The Transforming Growth Factor beta (TGF-β) signaling pathway plays a key role in GBM and is implicated in proliferation, invasion and therapy resistance. Several inhibitors of the TGF-β pathway have entered clinical trials or are under development...
October 10, 2016: Cancer Letters
Victoria E Pedanou, Stéphane Gobeil, Sébastien Tabariès, Tessa M Simone, Lihua Julie Zhu, Peter M Siegel, Michael R Green
Epithelial cells that lose attachment to the extracellular matrix undergo a specialized form of apoptosis called anoikis. Here, using large-scale RNA interference (RNAi) screening, we find that KDM3A, a histone H3 lysine 9 (H3K9) mono- and di-demethylase, plays a pivotal role in anoikis induction. In attached breast epithelial cells, KDM3A expression is maintained at low levels by integrin signaling. Following detachment, integrin signaling is decreased resulting in increased KDM3A expression. RNAi-mediated knockdown of KDM3A substantially reduces apoptosis following detachment and, conversely, ectopic expression of KDM3A induces cell death in attached cells...
2016: ELife
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