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Oncogenesis

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https://read.qxmd.com/read/30783098/an-fbxw7-zeb2-axis-links-emt-and-tumour-microenvironment-to-promote-colorectal-cancer-stem-cells-and-chemoresistance
#1
Ningning Li, Roya Babaei-Jadidi, Federica Lorenzi, Bradley Spencer-Dene, Philip Clarke, Enric Domingo, Eugene Tulchinsky, Robert G J Vries, David Kerr, Yihang Pan, Yulong He, David O Bates, Ian Tomlinson, Hans Clevers, Abdolrahman S Nateri
Colorectal cancer (CRC) patients develop recurrence after chemotherapy owing to the survival of stem cell-like cells referred to as cancer stem-like cells (CSCs). The origin of CSCs is linked to the epithelial-mesenchymal transition (EMT) process. Currently, it remains poorly understood how EMT programmes enable CSCs residing in the tumour microenvironment to escape the effects of chemotherapy. This study identifies a key molecular pathway that is responsible for the formation of drug-resistant CSC populations...
February 19, 2019: Oncogenesis
https://read.qxmd.com/read/30783083/a-negative-feedback-loop-between-xbp1-and-fbw7-regulates-cancer-development
#2
Unbin Chae, Heejin Lee, Bokyung Kim, Haiyoung Jung, Byeong Mo Kim, Ann- Hwee Lee, Dong-Seok Lee, Sang-Hyun Min
In cancer, activation of X-box binding protein (XBP1) has a critical role in tumorigenesis and cancer progression. Transcriptional regulatory mechanism of XBP1 in cancer development has been well known, however, regulation of ubiquitination and degradation of XBP1 has not been elucidated yet. Here we show that Fbw7, a substrate recognition component of the SKP1-Cullin-F-box-type E3 ligase, interacts with XBP1 in a phosphorylation-dependent manner, and facilitates XBP1 ubiquitination and protein degradation...
February 19, 2019: Oncogenesis
https://read.qxmd.com/read/30783079/dihydroartemisinin-inhibits-prostate-cancer-via-jarid2-mir-7-mir-34a-dependent-downregulation-of-axl
#3
Juliano D Paccez, Kristal Duncan, Durairaj Sekar, Ricardo G Correa, Yihong Wang, Xuesong Gu, Manoj Bashin, Kelly Chibale, Towia A Libermann, Luiz F Zerbini
Axl expression is deregulated in several cancer types, predicts poor overall patient survival and is linked to resistance to drug therapy. Here, we evaluated a library of natural compounds for inhibitors of Axl and identified dihydroartemisinin, the active principle of the anti-malarial drug artemisinin, as an Axl-inhibitor in prostate cancer. Dihydroartemisinin blocks Axl expression leading to apoptosis, decrease in cell proliferation, migration, and tumor development of prostate cancer cells. Dihydroartemisinin treatment synergizes with docetaxel, a standard of care in metastatic prostate cancer increasing overall survival of mice with human xenografts...
February 19, 2019: Oncogenesis
https://read.qxmd.com/read/30741938/most-canine-ameloblastomas-harbor-hras-mutations-providing-a-novel-large-animal-model-of-ras-driven-cancer
#4
Persiana S Saffari, Natalia Vapniarsky, Anna S Pollack, Xue Gong, Sujay Vennam, Andrew J Pollack, Frank J M Verstraete, Robert B West, Boaz Arzi, Jonathan R Pollack
Canine acanthomatous ameloblastomas (CAA), analogs of human ameloblastoma, are oral tumors of odontogenic origin for which the genetic drivers have remained undefined. By whole-exome sequencing, we have now discovered recurrent HRAS and BRAF activating mutations, respectively, in 63% and 8% of CAA. Notably, cell lines derived from CAA with HRAS mutation exhibit marked sensitivity to MAP kinase (MAPK) pathway inhibitors, which constrain cell proliferation and drive ameloblast differentiation. Our findings newly identify a large-animal spontaneous cancer model to study the progression and treatment of RAS-driven cancer...
February 11, 2019: Oncogenesis
https://read.qxmd.com/read/30723191/correction-lgr5-regulates-gastric-adenocarcinoma-cell-proliferation-and-invasion-via-activating-wnt-signaling-pathway
#5
Xiangfei Wang, Xiumin Wang, Yang Liu, Yating Dong, Yanan Wang, Muzaffer Ahmad Kassab, Wufang Fan, Xiaochun Yu, Chen Wu
The second corresponding author Dr. Xiaochun Yu is only affiliated with [3] Department of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, 1500 E. Duarte Rd, Duarte, CA 91010, USA. He is not affiliated with [1] College of Life Sciences, Hebei University, Baoding 071002 Hebei, China.
February 2, 2019: Oncogenesis
https://read.qxmd.com/read/30683932/trem2-acts-as-a-tumor-suppressor-in-hepatocellular-carcinoma-by-targeting-the-pi3k-akt-%C3%AE-catenin-pathway
#6
Wenqing Tang, Bei Lv, Biwei Yang, Yukai Chen, Feifei Yuan, Lijie Ma, She Chen, Si Zhang, Jinglin Xia
Triggering receptor expressed on myeloid cells 2 (TREM2) is involved in nonmalignant pathological processes. However, TREM2's function in malignant diseases, especially in hepatocellular carcinoma (HCC) remains unknown. In the present study, we report that TREM2 is a novel tumor suppressor in HCC. TREM2 expression was obviously decreased in hepatoma cells (especially metastatic HCC cells), and in most human HCC tissues (especially extrahepatic metastatic tumors). Reduced tumor TREM2 expression was correlated with poor prognosis of HCC patients, and with aggressive pathological features (BCLC stage, tumor size, tumor encapsulation, vascular invasion, and tumor differentiation)...
January 25, 2019: Oncogenesis
https://read.qxmd.com/read/30659170/blocking-cxcls-cxcr2-axis-in-tumor-stromal-interactions-contributes-to-survival-in-a-mouse-model-of-pancreatic-ductal-adenocarcinoma-through-reduced-cell-invasion-migration-and-a-shift-of-immune-inflammatory-microenvironment
#7
Makoto Sano, Hideaki Ijichi, Ryota Takahashi, Koji Miyabayashi, Hiroaki Fujiwara, Tomoharu Yamada, Hiroyuki Kato, Takuma Nakatsuka, Yasuo Tanaka, Keisuke Tateishi, Yasuyuki Morishita, Harold L Moses, Hiroyuki Isayama, Kazuhiko Koike
Pancreatic ductal adenocarcinoma (PDAC) is characterized by dense stromal reaction (desmoplasia). We have previously reported that mice with conditional KrasG12D mutation and knockout of TGF-β receptor type II (Tgfbr2), PKF mice, develop PDAC with desmoplasia modulated by CXC chemokines that are produced by PDAC cells through tumor-stromal interaction. In this study, we further discovered that PDAC and cancer-associated fibroblast (CAF) accelerated each other's invasion and migration through the CXC chemokines-receptor (CXCLs-CXCR2) axis...
January 18, 2019: Oncogenesis
https://read.qxmd.com/read/30647407/activation-of-c-met-in-cancer-cells-mediates-growth-promoting-signals-against-oxidative-stress-through-nrf2-ho-1
#8
Samik Chakraborty, Murugabaskar Balan, Evelyn Flynn, David Zurakowski, Toni K Choueiri, Soumitro Pal
Any imbalance between reactive oxygen species (ROS) generation and the anti-oxidant capacity lead to cellular oxidative stress. Many chemotherapeutic agents mediate their cytotoxic functions through the generation of ROS. c-Met, a receptor tyrosine kinase, is over-expressed in renal cancer and plays very crucial role(s) in its growth and survival. Here, we show that c-Met activation protected renal cancer cells from ROS, oxidative stress and cytotoxicity induced by the anti-cancer agent sorafenib (used for renal cancer treatment); and it markedly attenuated sorafenib-induced DNA damage...
January 15, 2019: Oncogenesis
https://read.qxmd.com/read/30643113/transactivation-of-human-endogenous-retroviruses-by-tumor-viruses-and-their-functions-in-virus-associated-malignancies
#9
REVIEW
Jungang Chen, Maryam Foroozesh, Zhiqiang Qin
Human endogenous retroviruses (HERVs), viral-associated sequences, are normal components of the human genome and account for 8-9% of our genome. These original provirus sequences can be transactivated to produce functional products. Several reactivated HERVs have been implicated in cancers and autoimmune diseases. An emerging body of literature supports a potential role of reactivated HERVs in viral diseases, in particular viral-associated neoplasms. Demystifying studies on the mechanism(s) of HERV reactivation could provide a new framework for the development of treatment and prevention strategies targeting virus-associated tumors...
January 14, 2019: Oncogenesis
https://read.qxmd.com/read/30631034/inhibition-of-hgf-met-signaling-decreases-overall-tumor-burden-and-blocks-malignant-conversion-in-tpl2-related-skin-cancer
#10
Nicole F Bonan, David Kowalski, Kaitie Kudlac, Kira Flaherty, J Curtis Gwilliam, Lauren G Falkenberg, Erik Maradiaga, Kathleen L DeCicco-Skinner
Tumor progression locus 2 (Tpl2) is a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family of serine/threonine kinases. Deletion of the Tpl2 gene is associated with a significantly higher number of papillomas and cutaneous squamous cell carcinomas (cSCCs). Overexpression of hepatocyte growth factor (HGF) and its receptor MET is abundant in cSCC and can lead to increased proliferation, migration, invasion or resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors...
January 10, 2019: Oncogenesis
https://read.qxmd.com/read/30631046/estrogen-receptor-%C3%AE-regulation-of-microrna-590-targets-fam171a1-a-modifier-of-breast-cancer-invasiveness
#11
Rahul Sanawar, Vipin Mohan Dan, Thankayyan R Santhoshkumar, Rakesh Kumar, M Radhakrishna Pillai
The pathobiology and aggressiveness of the triple negative breast cancer (TNBC) are influenced by genes that are preferentially expressed in TNBC cells. However, the nature of such genes with the role in invasiveness of TNBC cells is not fully understood. Here, we identified FAM171A1, member (A1) of the family with sequence similarity 171, as an overexpressed candidate gene in TNBC cells and tumors as compared to estrogen receptor-alpha (ERα) positive breast cancer. We found that the expression of FAM171A1 correlates well with the loss of ERα as well as its newly identified target miR590-5p in TNBC but not in ERα-positive cells...
January 9, 2019: Oncogenesis
https://read.qxmd.com/read/30631037/cullin-5-is-a-novel-candidate-tumor-suppressor-in-renal-cell-carcinoma-involved-in-the-maintenance-of-genome-stability
#12
María Ángeles Tapia-Laliena, Nina Korzeniewski, Samuel Peña-Llopis, Claudia Scholl, Stefan Fröhling, Markus Hohenfellner, Anette Duensing, Stefan Duensing
Clear cell renal cell carcinoma (ccRCC) is intimately associated with defects in ubiquitin-mediated protein degradation. Herein, we report that deficiency in the E3 ligase subunit cullin 5 (CUL5) promotes chromosomal instability and is an independent negative prognostic factor in ccRCC. CUL5 was initially identified in an RNA interference screen as a novel regulator of centrosome duplication control. We found that depletion of CUL5 rapidly promotes centriole overduplication and mitotic errors. Downregulation of CUL5 also caused an increase of DNA damage that was found to involve impaired DNA double-strand break repair...
January 9, 2019: Oncogenesis
https://read.qxmd.com/read/30631055/histone-demethylase-kdm6b-has-an-anti-tumorigenic-function-in-neuroblastoma-by-promoting-differentiation
#13
Liqun Yang, Yunhong Zha, Jane Ding, Bingwei Ye, Mengling Liu, Chunhong Yan, Zheng Dong, Hongjuan Cui, Han-Fei Ding
Induction of differentiation is a therapeutic strategy in high-risk neuroblastoma, a childhood cancer of the sympathetic nervous system. Neuroblastoma differentiation requires transcriptional upregulation of neuronal genes. How this process is regulated at epigenetic levels is not well understood. Here we report that the histone H3 lysine 27 demethylase KDM6B is an epigenetic activator of neuroblastoma cell differentiation. KDM6B mRNA expression is downregulated in poorly differentiated high-risk neuroblastomas and upregulated in differentiated tumors, and high KDM6B expression is prognostic for better survival in neuroblastoma patients...
January 4, 2019: Oncogenesis
https://read.qxmd.com/read/30631038/the-csn3-subunit-of-the-cop9-signalosome-interacts-with-the-hd-region-of-sos1-regulating-stability-of-this-gef-protein
#14
Natasha Zarich, Begoña Anta, Alberto Fernández-Medarde, Alicia Ballester, María Pilar de Lucas, Ana Belén Cámara, Berta Anta, José Luís Oliva, José M Rojas-Cabañeros, Eugenio Santos
Sos1 is an universal, widely expressed Ras guanine nucleotide-exchange factor (RasGEF) in eukaryotic cells. Its N-terminal HD motif is known to be involved in allosteric regulation of Sos1 GEF activity through intramolecular interaction with the neighboring PH domain. Here, we searched for other cellular proteins also able to interact productively with the Sos1 HD domain. Using a yeast two-hybrid system, we identified the interaction between the Sos1 HD region and CSN3, the third component of the COP9 signalosome, a conserved, multi-subunit protein complex that functions in the ubiquitin-proteasome pathway to control degradation of many cellular proteins...
January 4, 2019: Oncogenesis
https://read.qxmd.com/read/30573731/cd36-plays-a-critical-role-in-proliferation-migration-and-tamoxifen-inhibited-growth-of-er-positive-breast-cancer-cells
#15
Yu Liang, Hao Han, Lipei Liu, Yajun Duan, Xiaoxiao Yang, Chuanrui Ma, Yan Zhu, Jihong Han, Xiaoju Li, Yuanli Chen
Tamoxifen inhibits estrogen receptor (ER)-positive breast cancer growth while CD36 potentiates cancer metastasis. The effects of CD36 on proliferation/migration of breast cancer cells and tamoxifen-inhibited ER-positive cell growth are unknown. In this study, we correlated the mortality of breast cancer patients to tumor CD36 expression levels. We also found CD36 was higher in ER-rich (MCF-7>T-47D~ZR-75-30) than ER-negative (MDA-MB-231) cells. CD36 siRNA decreased viability and migration of MCF-7 and MDA-MB-231 cells with more potent effects on MCF-7 cells...
December 21, 2018: Oncogenesis
https://read.qxmd.com/read/30563983/mir-100-maintains-phenotype-of-tumor-associated-macrophages-by-targeting-mtor-to-promote-tumor-metastasis-via-stat5a-il-1ra-pathway-in-mouse-breast-cancer
#16
Wei Wang, Yan Liu, Jian Guo, Huiwen He, Xue Mi, Chong Chen, Junling Xie, Shengnan Wang, Peng Wu, Fengqi Cao, Lipeng Bai, Qin Si, Rong Xiang, Yunping Luo
Tumor-associated macrophages (TAMs), the main part of immune cells in tumor microenvironment (TME), play a potent role in promoting tumorigenesis through mechanisms such as stimulating angiogenesis, enhancing tumor migration and suppressing antitumor immunity. MicroRNAs (miRNAs) are considered as crucial regulators in multiple biological processes. The relationship between miRNAs and macrophages function has been extensively reported, but the roles that miRNAs play in regulating TAMs phenotype remain unclear...
December 19, 2018: Oncogenesis
https://read.qxmd.com/read/30563971/atypical-gata-transcription-factor-trps1-represses-gene-expression-by-recruiting-chd4-nurd-mta2-and-suppresses-cell-migration-and-invasion-by-repressing-tp63-expression
#17
Yuzhi Wang, Xue Lin, Xue Gong, Lele Wu, Jun Zhang, Weiguang Liu, Jian Li, Liming Chen
Transcriptional repressor GATA binding 1 (TRPS1), an atypical GATA transcription factor, functions as a transcriptional repressor and is also implicated in human cancers. However, the underlying mechanism of TRPS1 contributing to malignancy remains obscure. In the current study, we report that TRPS1 recognizes both gene proximal and distal transcription start site (TSS) sequences to repress gene expression. Co-IP mass spectrometry and biochemical studies showed that TRPS1 binds to CHD4/NuRD(MTA2). Genome-wide and molecular studies revealed that CHD4/NuRD(MTA2) is required for TRPS1 transcriptional repression...
December 19, 2018: Oncogenesis
https://read.qxmd.com/read/30518871/the-extracellular-sema-domain-attenuates-intracellular-apoptotic-signaling-of-semaphorin-6a-in-lung-cancer-cells
#18
Cheng-Ying Shen, Ya-Chu Chang, Li-Han Chen, Wen-Chun Lin, Yung-Hua Lee, Shu-Tsen Yeh, Hsin-Kuang Chen, Wentao Fang, Chung-Ping Hsu, Jang-Ming Lee, Tzu-Pin Lu, Pei-Wen Hsiao, Liang-Chuan Lai, Mong-Hsun Tsai, Eric Y Chuang
Semaphorin 6A (SEMA6A), a membrane-bound protein, is downregulated in lung cancer tissue compared to its adjacent normal tissue. However, the functions of SEMA6A in lung cancer cells are still unclear. In the present study, full length SEMA6A and various truncations were transfected into lung cancer cells to investigate the role of the different domains of SEMA6A in cell proliferation and survival, apoptosis, and in vivo tumor growth. SEMA6A-induced cell signaling was explored using gene silencing, co-immunoprecipitation, and co-culture assays...
December 5, 2018: Oncogenesis
https://read.qxmd.com/read/30478317/cbx2-identified-as-driver-of-anoikis-escape-and-dissemination-in-high-grade-serous-ovarian-cancer
#19
Lindsay J Wheeler, Zachary L Watson, Lubna Qamar, Tomomi M Yamamoto, Miriam D Post, Amber A Berning, Monique A Spillman, Kian Behbakht, Benjamin G Bitler
High grade serous ovarian carcinoma (HGSOC) is often diagnosed at an advanced stage. Chromobox 2 (CBX2), a polycomb repressor complex subunit, plays an oncogenic role in other cancers, but little is known about its role in HGSOC. We hypothesize that CBX2 upregulation promotes HGSOC via induction of a stem-like transcriptional profile and inhibition of anoikis. Examination of Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas (TCGA) established that increased CBX2 expression conveyed chemoresistance and worse disease-free and overall survival...
November 26, 2018: Oncogenesis
https://read.qxmd.com/read/30478303/ikk%C3%AE-activates-p53-to-promote-cancer-cell-adaptation-to-glutamine-deprivation
#20
Mari B Ishak Gabra, Ying Yang, Xazmin H Lowman, Michael A Reid, Thai Q Tran, Mei Kong
One of the hallmarks of cancer is the ability to reprogram cellular metabolism to increase the uptake of necessary nutrients such as glucose and glutamine. Driven by oncogenes, cancer cells have increased glutamine uptake to support their highly proliferative nature. However, as cancer cells continue to replicate and grow, they lose access to vascular tissues and deplete local supply of nutrients and oxygen. We previously showed that many tumor cells situate in a low glutamine microenvironment in vivo, yet the mechanisms of how they are able to adapt to this metabolic stress are still not fully understood...
November 26, 2018: Oncogenesis
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