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| Open AccessInduction of mitochondrial dysfunction as a strategy for targeting tumour cells in metabolically compromised microenvironments
Quiescent sub-populations of cells in tumours are resistant to traditional chemotherapeutics and are responsible for tumour recurrence. Here, Zhang et al. identify a compound that kills quiescent tumour cells in solid tumour tissue by inducing mitochondrial dysfunction.
- Xiaonan Zhang
- , Mårten Fryknäs
- & Stig Linder
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RSPO2–LGR5 signaling has tumour-suppressive activity in colorectal cancer
R-spondin 2 has an important role in development but its function in cancer has not been described. In this study, Wu et al. demonstrate that R-spondin 2 is decreased in expression in colorectal cancer and this is associated with promoter methylation and inhibition of Wnt signalling.
- Changjie Wu
- , Sunquan Qiu
- & Xincheng Lu
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SLAP displays tumour suppressor functions in colorectal cancer via destabilization of the SRC substrate EPHA2
SLAP is an adaptor protein that negatively regulates receptor signalling, but its involvement in cancer has not been described. In this study, Naudin et al. demonstrate that SLAP negatively regulates the receptor EphA2 in a Src-dependent manner and is reduced in expression in colorectal cancer.
- Cécile Naudin
- , Audrey Sirvent
- & Serge Roche
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The miR-363-GATA6-Lgr5 pathway is critical for colorectal tumourigenesis
Lgr5 is a protein that is important for the maintenance of intestinal homeostasis. In this study, the authors demonstrate that Lgr5 is required for colorectal cancer development and its expression is regulated by the transcription factor GATA6.
- Shinnosuke Tsuji
- , Yoshihiro Kawasaki
- & Tetsu Akiyama
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Whole exome sequencing of insulinoma reveals recurrent T372R mutations in YY1
Insulinomas develop from pancreatic β-cells and secrete insulin, but the underlying genetic defects are largely unknown. In this study, Cao et al. identify recurrent T372R mutations in the transcription factor YY1, and validate this hotspot mutation in 30% of insulinomas.
- Yanan Cao
- , Zhibo Gao
- & Guang Ning
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Article
| Open AccessWnt secretion is required to maintain high levels of Wnt activity in colon cancer cells
Activating mutations in the Wnt signalling pathway are associated with colon cancer. Here the authors show that tumour cells carrying mutations in APC and β-catenin are still regulated by Wnt ligands, suggesting that Wnt secretion and receptor signalling remains important to control downstream signalling.
- Oksana Voloshanenko
- , Gerrit Erdmann
- & Michael Boutros
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Article
| Open AccessAkt-p53-miR-365-cyclin D1/cdc25A axis contributes to gastric tumorigenesis induced by PTEN deficiency
The PTEN/Akt signalling pathway has been implicated in the pathogenesis of gastric cancer. Here, Guo et al. show that activation of Akt signalling results in the dysregulation of miR-365, which promotes tumorigenesis and that miR-365 reduction correlates with advance-stage tumours in gastric cancer patients.
- Shui-Long Guo
- , Hui Ye
- & Xiao Yang
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Switch of glycolysis to gluconeogenesis by dexamethasone for treatment of hepatocarcinoma
Hepatocytes use gluconeogenesis to produce glucose, but whether this process is altered in hepatocellular carcinoma (HCC) is unclear. Here, the loss of gluconeogenesis in HCC and altered glucocorticoid regulation is demonstrated and glucocorticoid treatment is shown to reduce tumour burden.
- Ruihua Ma
- , Wanguang Zhang
- & Bo Huang
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| Open AccessHigh frequency of telomerase reverse-transcriptase promoter somatic mutations in hepatocellular carcinoma and preneoplastic lesions
Telomerase reverse-trancriptase promoter mutations have been recently found in human melanomas. Here, Nault et al.identify telomerase reverse-trancriptase promoter mutations as the most frequent somatic genetic alterations in hepatocellular carcinomas and as the first mutation identified in cirrhotic preneoplastic lesions.
- Jean Charles Nault
- , Maxime Mallet
- & Jessica Zucman-Rossi
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Microbiota-derived lactate accelerates colon epithelial cell turnover in starvation-refed mice
Epithelial cells in the colon mainly use microbial fermentation products as energy sources. Here Okada et al. find that lactate produced by commensal Lactobacillus murinusregulates colonic epithelial cell proliferation and show that mice are more susceptible to carcinogens when refed after a period of starvation.
- Toshihiko Okada
- , Shinji Fukuda
- & Taeko Dohi
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Elevated oncofoetal miR-17-5p expression regulates colorectal cancer progression by repressing its target gene P130
Tumorigenesis has been likened to a form of cellular reversion to the embryonic state. Ma et al.identify a foetal miRNA as an oncogenic activator of the Wnt/β-catenin pathway in colorectal cancer, whose expression is negatively correlated with survival but is positively correlated with response to adjuvant chemotherapy.
- Yanlei Ma
- , Peng Zhang
- & Huanlong Qin
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Detection and differential diagnosis of colon cancer by a cumulative analysis of promoter methylation
Changes in the methylation pattern of gene promoters are hallmarks of certain cancers, such as colon cancer. Here Yang et al.identify and validate a set of genes and measure the cumulative methylation of promoters, which allows them to distinguish between two stages of colon cancer.
- Qiong Yang
- , Ying Dong
- & Shu Wang
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Article
| Open AccessAn intrinsically labile α-helix abutting the BCL9-binding site of β-catenin is required for its inhibition by carnosic acid
β-Catenin can be oncogenic but finding inhibitors has been a challenge. Here, five compounds are identified, which attenuate transcriptional β-catenin outputs in colorectal cancer cells, and the response to one of them is shown to require an intrinsically labile α-helix next to the BCL9-binding site in β-catenin.
- Marc de la Roche
- , Trevor J. Rutherford
- & Mariann Bienz
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MicroRNA122 is a key regulator of α-fetoprotein expression and influences the aggressiveness of hepatocellular carcinoma
α-fetoprotein is used as a biomarker of hepatocellular cancer but the mechanisms that lead to its elevated expression are unknown. Kojimaet al.show that microRNA122 and CUX1 are important for the regulation of α-fetoprotein and suggest that loss of microRNA122 leads to more aggressive liver cancer.
- Kentaro Kojima
- , Akemi Takata
- & Kazuhiko Koike
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Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer
Ageing associated diseases are the subject of intense study. In this article Serrano and colleagues demonstrate that Sirt1 over-expression in mice prevents both ageing associated diseases and liver cancer.
- Daniel Herranz
- , Maribel Muñoz-Martin
- & Manuel Serrano