Hot off the presses! Sep 01 Nat Rev Cancer

The Sep 01 issue of the Nat Rev Cancer is now up on Pubget (About Nat Rev Cancer): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

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  - Nat Rev Cancer 11(9):619 (2011)
  
• Metabolism: Flexible flux
  - Nat Rev Cancer 11(9):621 (2011)
  Although it is well known that many tumours exhibit increased glycolysis, less clear is how associated metabolic pathways are affected and whether they contribute to cancer cell proliferation. Using unbiased functional genomics and metabolomics methods, two groups have demonstrated the importance of the serine synthesis pathway and the enzyme phosphoglycerate dehydrogenase (PHGDH) for tumorigenesis.
• Tumorigenesis: Oncogene detox programme
  - Nat Rev Cancer 11(9):622 (2011)
  Reactive oxygen species (ROS) are known to promote tumour development through the mutation of both DNA and proteins. Gina DeNicola, David Tuveson and colleagues report contrasting data that indicate that the expression of classic oncogenes, such as KrasG12D, BrafV619E and Myc, reduces ROS levels and thereby facilitates tumour development.
• Therapy: Selective oxycution?
  - Nat Rev Cancer 11(9):622 (2011)
  One of the greatest challenges that is still to be widely addressed by anticancer therapies is the selective killing of cancer cells on the basis of cancer-specific features, rather than on generic properties that are shared with normal cells. New research shows that a natural product, piperlongumine, could have promising cancer-specific cytotoxicity.
• Screening of no use?
  - Nat Rev Cancer 11(9):622 (2011)
  Early detection of cancer is cited by many as our best route for tackling this disease, but a recent retrospective trend analysis published in the British Medical Journal indicates that mammography has not significantly contributed to reduced death rates from breast cancer.
• Immunology | Genetics | Cancer stem cells
  - Nat Rev Cancer 11(9):623 (2011)
  Platinum-based drugs disrupt STAT6-mediated suppression of immune responses against cancer in humans and mice Lesterhuis, W. J.et al. J. Clin. Invest.1 Aug 2011 (doi:10.1172/JCI43656)
• Microenvironment: Partners in crime
  - Nat Rev Cancer 11(9):624 (2011)
  When it comes to apportioning blame for metastasis, the finger usually points directly at tumour cells, but might these cells be coerced into their invasive behaviour? In a study published in Cell, Goetz, Del Pozo and co-workers outline how caveolin 1 (CAV1) that is expressed by stromal cells can promote tumour cell migration by remodelling the microenvironment.
• Metastasis: Opposing forces in invasion
  - Nat Rev Cancer 11(9):624 (2011)
  Understanding how cancer cells use the actin cytoskeleton to promote migration and invasion may provide insights into metastasis and potential therapeutic targets. Collapsin response mediator protein 1 (CRMP1; also known as DRP1), which has a known role in inducing depolymerization of actin filaments (F-actin) in neurons, has previously been shown to inhibit cancer cell invasion in vitro and to predict better outcomes in patients with non-small-cell lung cancer (NSCLC).
• Signalling | Therapy | Tumour suppressors | Biomarkers
  - Nat Rev Cancer 11(9):625 (2011)
  Translational repression of p53 by RNPC1, a p53 target overexpressed in lymphomas Zhang, J.et al. Genes Dev. 25, 1528–1543 (2011)
• Chromosomal instability: A lack of new origins drives fragility
  - Nat Rev Cancer 11(9):626 (2011)
  Chromosomal fragile sites initially came to the attention of the cancer research community because they were identified as sites of chromosomal breakpoints in tumours. Why these regions are more fragile than others has taken a while to sort out at the molecular level.
• Therapy: Modifying MYC expression
  - Nat Rev Cancer 11(9):626 (2011)
  Acute myeloid leukaemia (AML) is characterized by cooperative genetic and epigenetic alterations that promote tumorigenesis through various mechanisms, including the deregulation of differentiation programmes. Chromatin modifiers have been implicated in regulating such pathways; so, Lowe, Vakoc and colleagues carried out an RNA interference (RNAi) screen to identify key regulators of epigenetic modification in AML.
• Tumorigenesis: The origins of glioma
  - Nat Rev Cancer 11(9):627 (2011)
  The cell of origin for glioma has been an issue for discussion, with evidence pointing to neural stem cells (NSCs), or NSC-derived astrocytes or oligodendrocyte precursor cells (OPCs). Using mosaic mouse models, Liu and colleagues identify the cell of origin for glioma that is caused by inactivating mutations in neurofibromatosis 1 (Nf1) and Trp53.
• RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis
  - Nat Rev Cancer 11(9):629 (2011)
  The ubiquitin-proteasome system has numerous crucial roles in physiology and pathophysiology. Fundamental to the specificity of this system are ubiquitin-protein ligases (E3s). Of these, the majority are RING finger and RING finger-related E3s. Many RING finger E3s have roles in processes that are central to the maintenance of genomic integrity and cellular homeostasis, such as the anaphase promoting complex/cyclosome (APC/C), the SKP1–cullin 1–F-box protein (SCF) E3s, MDM2, BRCA1, Fanconi anaemia proteins, CBL proteins, von Hippel–Lindau tumour suppressor (VHL) and SIAH proteins. As a result, many RING finger E3s are implicated in either the suppression or the progression of cancer. This Review summarizes current knowledge in this area.
• MicroRNA regulation by RNA-binding proteins and its implications for cancer
  - Nat Rev Cancer 11(9):644 (2011)
  Non-protein-coding transcripts have been conserved throughout evolution, indicating that crucial functions exist for these RNAs. For example, microRNAs (miRNAs) have been found to modulate most cellular processes. The protein classes of RNA-binding proteins include essential regulators of miRNA biogenesis, turnover and activity. RNA–RNA and protein–RNA interactions are essential for post-transcriptional regulation in normal development and may be deregulated in disease. In reviewing emerging concepts of the interplay between miRNAs and RNA-binding proteins, we highlight the implications of these complex layers of regulation in cancer initiation and progression.
• What does physics have to do with cancer?
  - Nat Rev Cancer 11(9):657 (2011)
  Large-scale cancer genomics, proteomics and RNA-sequencing efforts are currently mapping in fine detail the genetic and biochemical alterations that occur in cancer. However, it is becoming clear that it is difficult to integrate and interpret these data and to translate them into treatments. This difficulty is compounded by the recognition that cancer cells evolve, and that initiation, progression and metastasis are influenced by a wide variety of factors. To help tackle this challenge, the US National Cancer Institute Physical Sciences-Oncology Centers initiative is bringing together physicists, cancer biologists, chemists, mathematicians and engineers. How are we beginning to address cancer from the perspective of the physical sciences?
• Dysregulated pH: a perfect storm for cancer progression
  - Nat Rev Cancer 11(9):671 (2011)
  Although cancer is a diverse set of diseases, cancer cells share a number of adaptive hallmarks. Dysregulated pH is emerging as a hallmark of cancer because cancers show a 'reversed' pH gradient with a constitutively increased intracellular pH that is higher than the extracellular pH. This gradient enables cancer progression by promoting proliferation, the evasion of apoptosis, metabolic adaptation, migration and invasion. Several new advances, including an increased understanding of pH sensors, have provided insight into the molecular basis for pH-dependent cell behaviours that are relevant to cancer cell biology. We highlight the central role of pH sensors in cancer cell adaptations and suggest how dysregulated pH could be exploited to develop cancer-specific therapeutics.
• O-GlcNAc signalling: implications for cancer cell biology
  - Nat Rev Cancer 11(9):678 (2011)
  O-GlcNAcylation is the covalent attachment of β-D-N-acetylglucosamine (GlcNAc) sugars to serine or threonine residues of nuclear and cytoplasmic proteins, and it is involved in extensive crosstalk with other post-translational modifications, such as phosphorylation. O-GlcNAcylation is becoming increasing realized as having important roles in cancer-relevant processes, such as cell signalling, transcription, cell division, metabolism and cytoskeletal regulation. However, currently little is known about the specific roles of aberrant O-GlcNAcylation in cancer. In this Opinion article, we summarize the current understanding of O-GlcNAcylation in cancer and its emerging functions in transcriptional regulation at the level of chromatin and transcription factors.
• Correspondence: Could platelet-accumulating polyphenols prevent tumour metastasis?
  - Nat Rev Cancer 11(9):685 (2011)
  We read with great interest the Review by Gay and Felding-Habermann (Contribution of platelets to tumour metastasis. Nature Rev. Cancer 11, 123–124 (2011)
• Advances in sarcoma genomics and new therapeutic targets
  - Nat Rev Cancer 11(9):685 (2011)
  In Table 2 of this article, there were errors in two of the cells. In the Sunitinib row, under the 'Tumour types' heading, "GIST" should have read "Imatinib-resistant GIST". Also in the Sunitinib row, under the 'Approximate response rate' heading, "80%" should have read "8%". This has now been corrected online.