BioEssays

Cover image for Vol. 37 Issue 9

Edited By: Andrew Moore

Online ISSN: 1521-1878

Cancer

Cancer

Cancer is a very heterogeneous disease, and this special collection takes a look at a wide variety of its features: from the mechanisms of metastasis, through a comparison of cancer cells with stem cells all the way to therapeutic opportunities. We hope you enjoy exploring these different aspects.



For primer literature of relevance to the articles below, see the Encyclopedia of Life SciencesELS_Logoentries Cell Biology of Cancer and Cancer Genetics.


Mouse models of colorectal cancer as preclinical models
Rebecca E. McIntyre, Simon J.A. Buczacki, Mark J. Arends and David J. Adams, BioEssays, Volume 37, Issue 8, August 2015, pages 909–920.
DOI: 10.1002/bies.201500032

colorectal cancer, disease biomarker, mouse model, ome and omics, target identification, target validation

Colorectal cancer is a heterogeneous disease, both genetically and epigenetically. Furthermore, tumour behaviour is strongly influenced by the micro-environment. Mouse modelling provides useful tools for validating therapeutic targets and providing mechanistic insights within the context of tumour diversity. Here we review the current repertoire of mouse models of colorectal cancer.


Bad luck and cancer: Does evolution spin the wheel of fortune?
Benjamin Roche, Beata Ujvari and Frédéric Thomas, BioEssays, Volume 37, Issue 5, June 2015, pages 586-587.
DOI: 10.1002/bies.201500012

cancer, evolution

Cancer is a complex disease, with sophisticated cellular mechanisms as the targets of evolutionary processes driven by random genetic and epigenetic mutations. Oncogenesis is evolutionarily linked to stem cell numbers/mutations and organ/body size; therefore, inter-disciplinary frameworks across different scales (cellular, tissue, organs and species) are necessary to decipher cancer progression.


Gut microbial metabolism and colon cancer: Can manipulations of the microbiota be useful in the management of gastrointestinal health?
Antoaneta Belcheva, Thergiory Irrazabal and Alberto Martin, BioEssays, Volume 37, Issue 4, April 2015, pages 403-412.
DOI: 10.1002/bies.201400175

colon cancer, dysbiosis, gut microbiota, metabolism

Microbial metabolism is essential in the maintenance of colonic homeostasis. Microbially-produced metabolites contribute to colon cancer development. Disrupting microbiota leads to dysbiosis and changes in the metabolic profile. Understanding the mechanisms through which metabolites drive cancer development is an essential step towards better management and treatment of colon cancer.


MAPping the Ndc80 loop in cancer: A possible link between Ndc80/Hec1 overproduction and cancer formation
Ngang Heok Tang and Takashi Toda, BioEssays, Volume 37, Issue 3, March 2015, pages 248-256.
DOI: 10.1002/bies.201400175

cancer, ch-TOG, Kinesin-8, loop, Ndc80/Hec1, overexpression, TACC

Mitotic chromosome mis-segregation leads to aneuploidy, the hallmark of cancer. Ndc80 kinetochore protein promotes cancer formation upon overproduction for some unknown reason. Here we propose that rather than a gain-of-function by overproduced Ndc80, abnormal sequestration of its binding proteins via the Ndc80 internal loop may exert causative impacts on tumourigenesis.


Do age-associated DNA methylation changes increase the risk of malignant transformation?
Wolfgang Wagner, Carola I. Weidner and Qiong Lin, BioEssays, Volume 37, Issue 1, January 2015, pages 20-24.
DOI: 10.1002/bies.201400063

aging, cancer, DNA-methylation, DNMT3A, epigenetics, epimutation, predictor

Age-predictors based on specific DNA-methylation (DNAm) changes reflect biological aging. The global changes in DNAm pattern may also trigger aberrant DNAm – so called epimutations – that can initiate tumor formation in the elderly. The figure is adopted from Waddington's “epigenetic landscape” (The Strategy of The Genes. London, Allan & Unwin 1957).


Lysine methylation in cancer: SMYD3-MAP3K2 teaches us new lessons in the Ras-ERK pathway
Paula Colón-Bolea and Piero Crespo, BioEssays, Volume 36, Issue 12, December 2014, pages 1162-1169.
DOI: 10.1002/bies.201400120

cancer, ERK, lysine methyltransferases, MAP3K2, Ras, SMYD3

Lysine methylation is traditionally associated with histones and epigenetics. Recently, lysine methyltransferases involved in methylation of non-histone substrates have been frequently found deregulated in tumours. Now methyltransferase SMYD3 has been identified as an enhancer of Ras-driven cancer via methylation of MAP3K2, which prevents it from binding to the phosphatase PP2A, thereby mitigating its negative regulation of Ras-ERK1/2 signals, hence promoting tumourigenesis.


How does oncogene transformation render tumor cells hypersensitive to nutrient deprivation?
Gabriel Leprivier and Poul H. Sorensen, BioEssays, Volume 36, Issue 11, November 2014, pages 1082-1090.
DOI: 10.1002/bies.201400085

eEF2 kinase, eEF2K, metabolic stress, mRNA translation elongation, oncogenes, stress signaling

Oncogene activation leads to hypersensitivity to nutrient deprivation by deregulation of specific metabolic pathways. Novel mechanisms underlying this phenotype are emerging, such as altered control of mRNA translation elongation by inhibition of the eEF2 kinase (eEF2K). The adaptive mechanisms used to circumvent oncogene-mediated cell death under nutrient deprivation are described.


Targeting cancer's weaknesses (not its strengths): Therapeutic strategies suggested by the atavistic model
Charles H. Lineweaver, Paul C.W. Davies and Mark D. Vincent, BioEssays, Volume 36, Issue 9, September 2014, pages 827-835.
DOI: 10.1002/bies.201400070

adaptive immunity, cancer therapy, carcinogenesis, evolution of multicellularity

In the atavistic model of cancer progression, tumor cell dedifferentiation is interpreted as a reversion to phylogenetically earlier capabilities. Phylostratigraphy can then help predict which capabilities cancer cells have lost, and these predictions can be translated into new target-the-weaknesses therapies. Our most detailed example involves the immune system.

Also watch the accompanying Video Abstract.


From promotion to management: The wide impact of bacteria on cancer and its treatment
Ernesto Perez-Chanona and Christian Jobin, BioEssays, Volume 36, Issue 7, July 2014, pages 658-664.
DOI: 10.1002/bies.201400015

cancer, chemotherapy, dysbiosis, intestinal microbiota, therapeutic efficacy

The intestinal microbiota plays an essential role in the maintenance of intestinal homeostasis, and disrupted microbial functions are often associated with intestinal pathology such as colorectal cancer (CRC). New findings demonstrate that the microbiota also influence the anti-tumor efficacy of chemotherapeutic drugs, suggesting a novel role for microbes in cancer management.


Evolutionarily conserved stress responses as potential anticancer therapeutic targets? (Comment on DOI 10.1002/bies.201300170)
Mark Vincent, BioEssays, Volume 36, Issue 6, June 2014, pages 544-545.
DOI: 10.1002/bies.201400054


Stress-induced cellular adaptive strategies: Ancient evolutionarily conserved programs as new anticancer therapeutic targets
Arcadi Cipponi and David M. Thomas, BioEssays, Volume 36, Issue 6, June 2014, pages 552-560.
DOI: 10.1002/bies.201300170

adaptive response, cancer, drug resistance, genomic instability, stress

Resistance to anticancer therapies is partly due to the mutagenic capacity of malignant cells, accelerating adaptation to selective pressures. Since similar phenomena have been observed in prokaryotes and primitive eukaryotes, we hypothesize that evolutionarily conserved mechanisms may regulate hypermutability in cancer cells in response to environmental stress, including drug therapy.


Can a minimal replicating construct be identified as the embodiment of cancer?
Ricard V. Solé, Sergi Valverde, Carlos Rodriguez-Caso and Josep Sardanyés, BioEssays, Volume 36, Issue 5, May 2014, pages 503-512.
DOI: 10.1002/bies.201300098

cancer, error threshold, microbial populations, minimal cell, mutator phenotype

Cancer cells on the edge. As they evolve towards a genomically unstable state, cancer cells become capable of overcoming selection barriers. However, high instability might have a critical limit, with a minimal network of interacting genes required to sustain tumour survival, on the edge between order and disorder.


DNA methylation reprogramming in cancer: Does it act by re-configuring the binding landscape of Polycomb repressive complexes?
James P. Reddington, Duncan Sproul and Richard Meehan, BioEssays, Volume 36, Issue 2, February 2014, pages 134-140.
DOI: 10.1002/bies.201300130

cancer epigenetics, DNA methylation, epigenomics, H3K27me3, Polycomb, reprogramming

DNA methylation patterns are subject to widespread reprogramming during cancer development, the implications of which for the regulation of the cancer genome are not fully understood. Here we discuss how DNA methylation reprogramming could influence transcriptional regulation in cancer cells by modifying the genome-wide targeting of the Polycomb repression system.


Unmasking risk loci: DNA methylation illuminates the biology of cancer predisposition
Dvir Aran and Asaf Hellman, BioEssays, Volume 36, Issue 2, February 2014, pages 184-190.
DOI: 10.1002/bies.201300119

cancer, common human disease, disease risk loci, DNA methylation, epigenomics, gene regulation, transcriptional enhancers

Tumor samples exhibit genetic and epigenetic variations across individuals. However, cancer-associated risk sequence alleles failed to reveal the link with the mechanism of cancer (left). Implementation of DNA methylation data helps to resolve the effect on drivers of cancer development, and hence to explains the biology of cancer susceptibility (right).


How does pheomelanin synthesis contribute to melanomagenesis?
Ann M. Morgan, Jennifer Lo and David E. Fisher, BioEssays, Volume 35, Issue 8, August 2013, pages 672-676.
DOI:10.1002/bies.201300020

melanoma, pheomelanin, pigmentation, reactive oxygen species

Pheomelanin synthesis is associated with melanoma formation, but the mechanism has not been fully elucidated. We hypothesize that pheomelanin promotes formation of genotoxic reactive oxygen species, and/or that pheomelanin synthesis consumes cellular glutathione stores.


Pegylated IL-10 induces cancer immunity
John B. Mumm and Martin Oft, BioEssays, Volume 35, Issue 7, July 2013, pages 623-631.
DOI:10.1002/bies.201300004

cancer immune therapy, CD8+ T cells, cytotoxic T cells, IFN-gamma, major histocompatibility complex, pegylated IL-10

Pegylated IL-10 induces several essential components for cancer immunity: expansion of tumor resident CD8+ T cells, expression of IFN-γ and cytotoxic enzymes in tumor resident CD8+ T cells and antigen presentation within the tumor. PEG-IL-10 treatment leads to tumor rejection and long lasting tumor immunity.


Pausing for thought: Disrupting the early transcription elongation checkpoint leads to developmental defects and tumourigenesis
Barbara H. Jennings, BioEssays, Volume 35, Issue 6, June 2013, pages 553-560.
DOI:10.1002/bies.201200179

DSIF, NELF, promoter proximal pausing, P-TEFb, Spt5, transcription elongation

Animal studies reveal that correct regulation of promoter proximal pausing is critical for a diverse range of biological pathways during embryo development and also for health in adult life. This regulation facilitates fine control of gene expression levels and may also act as a barrier to uncontrolled cell proliferation.


Epithelial cell translocation: New insights into mechanisms of tumor initiation
Cheuk T. Leung, BioEssays, Volume 35, Issue 2, February 2013, pages 80-83.
DOI:10.1002/bies.201200151

epithelial tissue, organotypic culture, tissue homeostasis, tumorigenesis, tumor initiation

A cell translocation mechanism displaces sporadic mutant cells from normal, suppressive epithelial environment during early steps of tumor initiation. This epithelial cell translocation process exerts a selective pressure on early mutant cells to survive and grow in new microenvironment outside of their native niches.



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