Modeling Cutaneous Squamous Carcinoma Development in the Mouse

Huang, Pamela; Balmain, Allan

doi:10.1101/cshperspect.a013623

Cited by 34 publications

(25 citation statements)

References 154 publications

(151 reference statements)

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“…In this study, we compared tumor series with different fates through analysis of a DMBA-TPA carcinogenesis protocol. Although the DMBA-TPA protocol is limited to the analysis of the tumors initiated by RAS family mutation, it is widely accepted that the mutation landscape, mutation burden, and gene expression profile of the SCCs formed on the mouse back skin through the DMBA-TPA protocol are largely similar to human SCCs such as head and neck, esophageal, lung, and cervical SCCs 14 , 17 , 18 , 36 , 37 . In line with these previous studies, our results indicated that although the carcinogenesis protocol using DMBA-TPA provides information on the initial driver mutations and promotes the formation of a number of papillomas on the mouse skin, further drivers are clearly required for the malignant alteration.…”

Section: Discussionmentioning

confidence: 99%

“…SCC is one of the most common cancers in Caucasian populations, and the prognosis of metastatic SCC is extremely poor 14 . The DMBA-induced SCC model is one of the most commonly used in vivo models and is widely used for studying the mechanisms of metastasis 15 , which can be applied to both human and mouse cancers 14 , 16 . High-throughput genome sequencing analysis has previously been conducted for DMBA-induced mouse skin SCCs 17 , 18 .…”

Section: Introductionmentioning

confidence: 99%

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Time-Series Analysis of Tumorigenesis in a Murine Skin Carcinogenesis Model

Aoto

Okumura

Hachiya

et al. 2018

Sci Rep

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Recent years have witnessed substantial progress in understanding tumor heterogeneity and the process of tumor progression; however, the entire process of the transition of tumors from a benign to metastatic state remains poorly understood. In the present study, we performed a prospective cancer genome-sequencing analysis by employing an experimental carcinogenesis mouse model of squamous cell carcinoma to systematically understand the evolutionary process of tumors. We surgically collected a part of a lesion of each tumor and followed the progression of these tumors in vivo over time. Comparative time-series analysis of the genomes of tumors with different fates, i.e., those that eventually metastasized and regressed, suggested that these tumors acquired and inherited different mutations. These findings suggest that despite the occurrence of an intra-tumor selection event for malignant alteration during the transformation from early- to late-stage papilloma, the fate determination of tumors might be determined at an even earlier stage.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Time-Series Analysis of Tumorigenesis in a Murine Skin Carcinogenesis Model

Aoto

Okumura

Hachiya

et al. 2018

Sci Rep

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“…Using this cohort, we induced skin tumors using the chemical carcinogen 7,12-Dimethylbenz(a)anthracene (DMBA) and the tumor promoting agent 12-O-Tetradecanoylphorbol-13-acetate (TPA) [ 7 ]. This protocol initially results in the formation of benign papillomas, a fraction of which will progress into carcinomas.…”

Section: Introductionmentioning

confidence: 99%

Panx3 links body mass index and tumorigenesis in a genetically heterogeneous mouse model of carcinogen-induced cancer

et al. 2016

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BackgroundBody mass index (BMI) has been implicated as a primary factor influencing cancer development. However, understanding the relationship between these two complex traits has been confounded by both environmental and genetic heterogeneity.MethodsIn order to gain insight into the genetic factors linking BMI and cancer, we performed chemical carcinogenesis on a genetically heterogeneous cohort of interspecific backcross mice ((Mus Spretus × FVB/N) F1 × FVB/N). Using this cohort, we performed quantitative trait loci (QTL) analysis to identify regions linked to BMI. We then performed an integrated analysis incorporating gene expression, sequence comparison between strains, and gene expression network analysis to identify candidate genes influencing both tumor development and BMI.ResultsAnalysis of QTL linked to tumorigenesis and BMI identified several loci associated with both phenotypes. Exploring these loci in greater detail revealed a novel relationship between the Pannexin 3 gene (Panx3) and both BMI and tumorigenesis. Panx3 is positively associated with BMI and is strongly tied to a lipid metabolism gene expression network. Pre-treatment Panx3 gene expression levels in normal skin are associated with tumor susceptibility and inhibition of Panx function strongly influences inflammation.ConclusionsThese studies have identified several genetic loci that influence both BMI and carcinogenesis and implicate Panx3 as a candidate gene that links these phenotypes through its effects on inflammation and lipid metabolism.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-016-0334-8) contains supplementary material, which is available to authorized users.

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“…In mice, the RAS–MAPK pathway is essential for benign tumours and SCCs 7 . Downstream of RAS G12V –MAPK is SOX2, an essential transcription factor induced by SCC-initiating (stem) cells 8–11 .…”

mentioning

confidence: 99%

Translation from unconventional 5′ start sites drives tumour initiation

Sendoel

Dunn

Rodriguez

et al. 2017

Nature

306

375

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We are just beginning to understand how translational control affects tumour initiation and malignancy. Here we use an epidermis-specific, in vivo ribosome profiling strategy to investigate the translational landscape during the transition from normal homeostasis to malignancy. Using a mouse model of inducible SOX2, which is broadly expressed in oncogenic RAS-associated cancers, we show that despite widespread reductions in translation and protein synthesis, certain oncogenic mRNAs are spared. During tumour initiation, the translational apparatus is redirected towards unconventional upstream initiation sites, enhancing the translational efficiency of oncogenic mRNAs. An in vivo RNA interference screen of translational regulators revealed that depletion of conventional eIF2 complexes has adverse effects on normal but not oncogenic growth. Conversely, the alternative initiation factor eIF2A is essential for cancer progression, during which it mediates initiation at these upstream sites, differentially skewing translation and protein expression. Our findings unveil a role for the translation of 5′ untranslated regions in cancer, and expose new targets for therapeutic intervention.

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Modeling Cutaneous Squamous Carcinoma Development in the Mouse

Cited by 34 publications

References 154 publications

Time-Series Analysis of Tumorigenesis in a Murine Skin Carcinogenesis Model

Time-Series Analysis of Tumorigenesis in a Murine Skin Carcinogenesis Model

Panx3 links body mass index and tumorigenesis in a genetically heterogeneous mouse model of carcinogen-induced cancer

Translation from unconventional 5′ start sites drives tumour initiation

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