Hot off the presses! Jun 01 Nat Rev Cancer

The Jun 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:

• From the editors
  - Nat Rev Cancer 10(6):379 (2010)
  MicroRNAs (miRNAs; small, non-coding RNAs) have progressed from relative obscurity to prime movers in cancer research in less than 10 years. The interest in miRNAs stems from their capacity to modify the expression of mRNAs that are crucial for cell homeostasis and recent data indicating their possible therapeutic use in the treatment of cancer.
• Signalling: Of Rags and Ragulator
  - Nat Rev Cancer 10(6):381 (2010)
  The mammalian target of rapamycin complex 1 (mTORC1) kinase regulates cell growth in response to growth factors, energy levels and amino acid availability, and is activated by RHEB, a Ras-related GTP-binding protein. Rag GTPases are amino acid-specific regulators of the mTORC1 pathway, but how they regulate mTORC1 was unknown.
• Tumour suppression: Double act
  - Nat Rev Cancer 10(6):382 (2010)
  Loss of the tumour suppressor gene BRCA1 is selected for in some spontaneous breast cancers and is associated with a more aggressive phenotype — oestrogen receptor (ER), progesterone receptor (PR) and ERBB2-negative breast cancer. Other spontaneous breast cancers can present with a similar triple negative phenotype, but with no disruption of BRCA1 evident.
• Screening saves lives
  - Nat Rev Cancer 10(6):382 (2010)
  A single 5 minute test for bowel cancer could save thousands of lives by detecting early cancerous polyps, prompting researchers to argue that it should be incorporated into current screening programmes.These findings were published in The Lancet by a team at Imperial College, London, UK, who examined 200,000 participants aged 55–64 over 10 years.
• Metastasis: A FASCINating block
  - Nat Rev Cancer 10(6):382 (2010)
  Migrastatin — an organic compound naturally occurring in Streptomyces platensis — and its synthetic analogues block tumour cell migration and inhibit metastasis; however, their mode of action is not clear. Xin-Yun Huang and colleagues now report in Nature that the migrastatin analogue macroketone inhibits tumour cell migration and metastasis by binding the actin-bundling protein fascin 1 (FSCN1) and blocking its activity.
• Immunology: The inflammasome protects?
  - Nat Rev Cancer 10(6):383 (2010)
  Inflammatory bowel disease (IBD) increases the risk of developing colorectal cancer (CRC) and is a good example of the link between inflammation and cancer in the gastrointestinal tract. Several molecular players, including the Toll-like family of pattern recognition receptors (PRRs), have emerged as mediatorsof IBD andCRC.
• Metastasis: How do you spell metastasis?
  - Nat Rev Cancer 10(6):384 (2010)
  The biology of metastasis and how cells are able to break free from the primary tumour and colonize distant sites is becoming increasingly understood; however, the genetic changes that govern this process are still not clear. A key question remains: are metastases the result of a small number of primary tumour cells acquiring certain genetic changes that allow them to spread or are they driven by oncogenic mutations that exist in most cells of a primary tumour?
• Therapy: Drugs hitch a ride
  - Nat Rev Cancer 10(6):384 (2010)
  A limitation of many anticancer drugs is their inability to target and penetrate tumour tissue, leading to reduced efficacy and nonspecific adverse effects on normal cells. In a study published in Science, researchers led by Erkki Ruoslahti have identified a method of specifically targeting drugs to the extravascular tumour tissue, and they show that this increases drug potency.
• In brief: Genomics, Tumorigenesis, Metabolism, Breast cancer
  - Nat Rev Cancer 10(6):384 (2010)
  High-risk myeloma is associated with global elevation of miRNA and overexpression of EIF2C2/AGO2 Zhou, Y.et al. Proc. Natl Acad. Sci. USA 107, 7904–7909 (2010)
• Statins lose prevention ground
  - Nat Rev Cancer 10(6):385 (2010)
  Epidemiological and clinical trial data have indicated that the cholesterol-lowering agents statins might protect against the development of several different types of cancer, including colorectal cancer. However, results from a planned secondary analysis of the Adenoma Prevention with Celecoxib (APC) trial have not upheld these findings.
• Signalling: Regulation and crosstalk
  - Nat Rev Cancer 10(6):386 (2010)
  The expansion of the Salvador (SAV)–Warts (WTS)–Hippo (HPO) pathway continues with three recent papers that extend the list of upstream regulators and identify links to Wnt signalling.Helena Richardson and colleagues had previously noted that loss-of-function of the tumour suppressor Lethal (2) giant larvae (L2GL) in the developing eye of Drosophila melanogaster results in aberrant proliferation and cell survival.
• Cancer stem cells: Wnt — looking outside in
  - Nat Rev Cancer 10(6):386 (2010)
  The Wnt signalling pathway drives stem cell self-renewal and is deregulated in most colon cancers; however, only a small proportion of colon cancer cells with Wnt-activating mutations have stem cell-like properties. Data from Medema and colleagues indicate that there is more to learn about the association between Wnt, stemness and the tumour microenvironment.
• Transcriptomics: Common disease pathogenesis pathways
  - Nat Rev Cancer 10(6):387 (2010)
  Several observations indicate that various human diseases might be biologically connected. In particular, some data suggest that metabolic, inflammatory and autoimmune diseases increase the risk of developing cancer, so Kevin Struhl and colleagues investigated whether their underlying biology overlaps.
• Genetic variation in microRNA networks: the implications for cancer research
  - Nat Rev Cancer 10(6):389 (2010)
  Many studies have highlighted the role that microRNAs have in physiological processes and how their deregulation can lead to cancer. More recently, it has been proposed that the presence of single nucleotide polymorphisms in microRNA genes, their processing machinery and target binding sites affects cancer risk, treatment efficacy and patient prognosis. In reviewing this new field of cancer biology, we describe the methodological approaches of these studies and make recommendations for which strategies will be most informative in the future.
• Helicobacter pylori: gastric cancer and beyond
  - Nat Rev Cancer 10(6):403 (2010)
  Helicobacter pylori is the dominant species of the human gastric microbiome, and colonization causes a persistent inflammatory response. H. pylori-induced gastritis is the strongest singular risk factor for cancers of the stomach; however, only a small proportion of infected individuals develop malignancy. Carcinogenic risk is modified by strain-specific bacterial components, host responses and/or specific host–microbe interactions. Delineation of bacterial and host mediators that augment gastric cancer risk has profound ramifications for both physicians and biomedical researchers as such findings will not only focus the prevention approaches that target H. pylori-infected human populations at increased risk for stomach cancer but will also provide mechanistic insights into inflammatory carcinomas that develop beyond the gastric niche.
• TGFβ signalling: a complex web in cancer progression
  - Nat Rev Cancer 10(6):415 (2010)
  The distortion of growth factor signalling is the most important prerequisite in tumour progression. Transforming growth factor-β (TGFβ) signalling regulates tumour progression by a tumour cell-autonomous mechanism or through tumour–stroma interaction, and has either a tumour-suppressing or tumour-promoting function depending on cellular context. Such inherent complexity of TGFβ signalling results in arduous, but promising, assignments for developing therapeutic strategies against malignant tumours. As numerous cellular context-dependent factors tightly maintain the balance of TGFβ signalling and contribute to the regulation of TGFβ-induced cell responses, in this Review we discuss how they maintain the balance of TGFβ signalling and how their collapse leads to tumour progression.
• The colony-stimulating factors and cancer
  - Nat Rev Cancer 10(6):425 (2010)
  The four colony-stimulating factors (CSFs) are glycoproteins that regulate the generation and some functions of infection-protective granulocytes and macrophages. Recombinant granulocyte-CSF (G-CSF) and granulocyte–macrophage-CSF (GM-CSF) have now been used to increase dangerously low white blood cell levels in many millions of cancer patients following chemotherapy. These CSFs also release haematopoietic stem cells to the peripheral blood, and these cells have now largely replaced bone marrow as more effective populations for transplantation to cancer patients who have treatment-induced bone marrow damage.
• Implications and challenges of connexin connections to cancer
  - Nat Rev Cancer 10(6):435 (2010)
  The idea that the gap junction family of proteins, connexins, are tumour suppressors has been widely supported through numerous cancer models. However, the paradigm that connexins and enhanced gap junctional intercellular communication is of universal benefit by restricting tumour growth has been challenged by more recent evidence that suggests a role for connexins in facilitating tumour progression and metastasis. Therefore, connexins might be better classified as conditional tumour suppressors that modulate cell proliferation, as well as adhesion and migration.
• Cell line misidentification: the beginning of the end
  American Type Culture Collection Standards Development Organization Workgroup ASN-0002 Masters JR - Nat Rev Cancer 10(6):441 (2010)
  Cell lines are used extensively in research and drug development as models of normal and cancer tissues. However, a substantial proportion of cell lines is mislabelled or replaced by cells derived from a different individual, tissue or species. The scientific community has failed to tackle this problem and consequently thousands of misleading and potentially erroneous papers have been published using cell lines that are incorrectly identified. Recent efforts to develop a standard for the authentication of human cell lines using short tandem repeat profiling is an important step to eradicate this problem.