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| Open AccessContribution of pks+ E. coli mutations to colorectal carcinogenesis
Common driver mutations in colorectal cancer (CRC) are not always consistent with frequent mutational signatures. Here, the authors analyse spatially annotated colon crypts in CRC patients and find mutational signatures of pks+ E. coli that are consistent with driver mutations, suggesting a potential role of pks+ E. coli in carcinogenesis.
- Bingjie Chen
- , Daniele Ramazzotti
- & Andrea Sottoriva
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Article
| Open AccessGut insulin action protects from hepatocarcinogenesis in diabetic mice comorbid with nonalcoholic steatohepatitis
Diabetes is known to increase the risk of nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Here, the authors show in a mice model that insulin action in the gut may play a protective role in the development of NASH and HCC in diabetes.
- Kotaro Soeda
- , Takayoshi Sasako
- & Kohjiro Ueki
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Article
| Open AccessEnrichment and sensing tumor cells by embedded immunomodulatory DNA hydrogel to inhibit postoperative tumor recurrence
Decreased survival after surgery is often associated to post-operative tumor recurrence and metastasis. Here the authors describe a DNA hydrogel enabling monitoring of tumor recurrence and spatiotemporally controlled photodynamic immunotherapy to prevent post-operative tumor recurrence and metastasis.
- Danyu Wang
- , Jingwen Liu
- & Kaixiang Zhang
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Article
| Open AccessMutant APC reshapes Wnt signaling plasma membrane nanodomains by altering cholesterol levels via oncogenic β-catenin
Dynamic proteolipid nanoassemblies at the plasma membrane of colonocytes serve as Wnt signaling hubs. Here, the authors find a role for mutant APC in colorectal cancer in the dysregulation of plasma membrane sterol homeostasis.
- Alfredo Erazo-Oliveras
- , Mónica Muñoz-Vega
- & Robert S. Chapkin
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Comment
| Open AccessBioengineering of bacteria for cancer immunotherapy
Here, we provide a brief overview of the approaches and strategies underlying bacteria-based cancer immunotherapy (BCiT). We also describe and summarize research in the field of synthetic biology, which aims to regulate bacterial growth and gene expression for immunotherapeutic use. Finally, we discuss the current clinical status and limitations of BCiT.
- Dinh-Huy Nguyen
- , Ari Chong
- & Jung-Joon Min
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Article
| Open AccessProtein stabilization of ITF2 by NF-κB prevents colitis-associated cancer development
NF-κB activation contributes to colitis-associated colorectal cancer (CAC). Here the authors show that NF-κB subunit, p65 stabilizes ITF2, which then suppresses NF-κB downstream genes and inhibits CAC progression.
- Mingyu Lee
- , Yi-Sook Kim
- & Hyun-Woo Shin
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Article
| Open AccessBreast cancer prevention by short-term inhibition of TGFβ signaling
TGFβ signalling is reported to regulate hormone-responsive mammary epithelial progenitors that are associated with breast cancer risk. Here, the authors find that short-term TGFBR1 inhibition prevents tumour formation in rat breast cancer models and identify a TGFBR1 inhibition-responsive sub-population of mammary epithelial cells, which is associated with human breast cancer risk.
- Maša Alečković
- , Simona Cristea
- & Kornelia Polyak
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Article
| Open AccessEvaluating cancer etiology and risk with a mathematical model of tumor evolution
Modelling how endogenous mutations accumulate in tissues is valuable to understand how cancers develop and evolve. Here, the authors establish a mathematical model that can predict the number of endogenous somatic mutations in the lifetime of tissues and approximate the time to cancer development.
- Sophie Pénisson
- , Amaury Lambert
- & Cristian Tomasetti
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Article
| Open AccessReversible Myc hypomorphism identifies a key Myc-dependency in early cancer evolution
Happloinsufficiency of Myc delays onset of cancers in mice. Here, the authors generated a mouse model of reversible cMyc hypomorphism and show that metronomic reduction of c-Myc in adult mice confers protection against cancers without side effects and that the bottleneck in early cancer evolution is dependent upon Myc.
- Nicole M. Sodir
- , Luca Pellegrinet
- & Gerard I. Evan
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Article
| Open AccessPeptide nano-blanket impedes fibroblasts activation and subsequent formation of pre-metastatic niche
Primary tumors “spread the spark” by establishing a pre-metastatic niche. Here the authors develop an in-situ assembled peptide FR17 to serve as a “flame-retarding blanket” to extinguish the “fire” of the pre-metastatic microenvironment.
- Yi Zhou
- , Peng Ke
- & Jianqing Gao
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Article
| Open AccessA microRNA panel compared to environmental and polygenic scores for colorectal cancer risk prediction
Appropriate risk models could facilitate risk stratification for colorectal cancer (CRC) screening. Here, the authors propose a blood-based microRNA signature observed to have altered expression in pre-diagnostic samples, which might be useful to identify high-risk populations for colorectal cancer screening.
- Janhavi R. Raut
- , Ben Schöttker
- & Hermann Brenner
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Article
| Open AccessEGCG binds intrinsically disordered N-terminal domain of p53 and disrupts p53-MDM2 interaction
Epigallocatechin gallate (EGCG) is a catechin flavonoid which induces apoptosis in cancerous cells, but the underlying molecular mechanisms remain poorly understood. Here authors use an interdisciplinary approach to show a direct interaction between EGCG and the tumor suppressor p53 and demonstrate that EGCG inhibits ubiquitination of p53 by MDM2.
- Jing Zhao
- , Alan Blayney
- & Chunyu Wang
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Article
| Open AccessA comprehensive re-assessment of the association between vitamin D and cancer susceptibility using Mendelian randomization
Studies of the genetic association between vitamin D and cancer risk have typically been underpowered. Here the authors analyse this using Mendelian Randomisation with more than 70 vitamin D variants obtained from the UK Biobank and large-scale data from various consortia, confirming null associations between vitamin D and most cancers.
- Jue-Sheng Ong
- , Suzanne C. Dixon-Suen
- & Stuart MacGregor
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Article
| Open AccessA multivariable Mendelian randomization analysis investigating smoking and alcohol consumption in oral and oropharyngeal cancer
Alcohol and smoking are both associated with oral/oropharyngeal cancer risk, but independent effects are unclear given their relatedness. Here, the authors use multivariable Mendelian randomization to show that both alcohol and smoking are independently causal for oral/oropharyngeal cancer.
- Mark Gormley
- , Tom Dudding
- & Rebecca C. Richmond
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Article
| Open AccessDeep transfer learning for reducing health care disparities arising from biomedical data inequality
Developing machine learning models that work equally well for all ethnic groups is of crucial importance to health disparity prevention and reduction. Here, using an extensive set of machine learning experiments on cancer omics data, the authors find that transfer learning can improve model performance for data-disadvantaged ethnic groups.
- Yan Gao
- & Yan Cui
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Article
| Open AccessImmunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer
Current preclinical models to investigate human HR + breast cancer progression and response to immunotherapy in vivo are limited. Here, the authors demonstrate that mammary tumours driven by a synthetic progestin combined with an oral carcinogen recapitulate several immunobiological features of human HR + breast cancers.
- Aitziber Buqué
- , Norma Bloy
- & Lorenzo Galluzzi
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Article
| Open AccessGermline variant burden in cancer genes correlates with age at diagnosis and somatic mutation burden
Germline variants that affect the expression or function of protein-coding regions of cancer genes are associated with cancer susceptibility. Here, the authors show that a larger number of germline variants are present in early-onset cancers, while acquired somatic mutations are prevalent in cancers that develop at older age.
- Tao Qing
- , Hussein Mohsen
- & Lajos Pusztai
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Article
| Open AccessThe vaginal microbiota associates with the regression of untreated cervical intraepithelial neoplasia 2 lesions
Persistent infection with human papillomavirus can lead to cervical intraepithelial neoplasia (CIN). Here, the authors profile the vaginal microbiota in a cohort of non-pregnant young women diagnosed with CIN2 and find that absence of Lactobacillusspp. and presence of a diverse population of strict anaerobes associates with a decreased regression of untreated CIN2 lesions.
- Anita Mitra
- , David A. MacIntyre
- & Maria Kyrgiou
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Comment
| Open AccessUntangling the evolutionary roots of lung cancer
The genomic and host factors that drive the progression of pre-invasive lesions in non-small cell lung cancer are poorly understood. Studying these factors can advance our knowledge of lung cancer biology, aid in the development of better screening strategies and improve patient outcomes.
- Siddhartha Devarakonda
- & Ramaswamy Govindan
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Article
| Open AccessABCB1 protects bat cells from DNA damage induced by genotoxic compounds
Bats possess an extended lifespan compared to most mammals of their size, and have a low cancer incidence. Here the authors show that several bat species exhibit resistance to genotoxic agents that is in part attributable to high expression of the ABCB1 transporter.
- Javier Koh
- , Yoko Itahana
- & Koji Itahana
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Article
| Open AccessPrevention of pancreatic acinar cell carcinoma by Roux-en-Y Gastric Bypass Surgery
Pancreatic cancer risk increases in obese and diabetic people. In this manuscript, the authors show that Roux-en-Y gastric bypass surgery (RYGB) decreases the impact of pancreatic cancer in a mouse model; this effect seems independent of weight loss or decreased hyperglycemia pointing to an involvement of mTOR pathway.
- Rui He
- , Yue Yin
- & Weizhen Zhang
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Article
| Open AccessA Mendelian randomization study of the effects of blood lipids on breast cancer risk
The link between circulating lipids and breast cancer risk is complex. Here, the authors utilise data from more than 400,000 participants in two-sample Mendelian randomization to assess the link between blood lipids and breast cancer risk, and they find risk-promoting effects of raised LDL-cholesterol and CETP-mediated raised HDL-cholesterol.
- Christoph Nowak
- & Johan Ärnlöv
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Perspective
| Open AccessEvaluating intrinsic and non-intrinsic cancer risk factors
Understanding the contributions of extrinsic and intrinsic factors on cancer risk is fundamental in determining the intervention and prevention strategies to tackle cancer. Here the authors provide a review of the different factors impacting cancer risk and discuss the limitations of different approaches in evaluating the relative contributions of these factors.
- Song Wu
- , Wei Zhu
- & Yusuf A Hannun
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Article
| Open AccessNuclear Smad6 promotes gliomagenesis by negatively regulating PIAS3-mediated STAT3 inhibition
In glioma STAT3 signaling contributes to gliomagenesis. Here, the authors show that Smad6 expression correlates with poor survival and is overexpressed in glioma cells, and regulates STAT3 activity via negatively regulating PIAS3.
- Jiantong Jiao
- , Rui Zhang
- & Zhaohui Huang
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Article
| Open AccessMutational signatures of ionizing radiation in second malignancies
Ionizing radiation may induce irreparable DNA damage leading to cancer. Here, the authors identify a specific signature of mutations arising in patients exposed to ionizing radiation and suggest that radiation-induced tumorigenesis is associated with higher rates of genome-wide deletions and balanced inversions.
- Sam Behjati
- , Gunes Gundem
- & Peter J. Campbell
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Article
| Open AccessInflammation driven by tumour-specific Th1 cells protects against B-cell cancer
Inflammation can result in the formation of tumours, but the immune system is also involved in the elimination of cancer cells. Here, the authors show that inflammation driven by tumour-specific CD4+T cells results in tumour regression and identify a list of cytokines associated with cancer prevention.
- Ole Audun Werner Haabeth
- , Kristina Berg Lorvik
- & Alexandre Corthay