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This Week in Cancer Cell: Dec 2, 2011


In Cancer Cell this week, researchers in Australia and the US report that PTEN loss and tumorigenesis can result when tumor suppressor GRHL3 is targeted by an miR-21-dependent proto-oncogenic network. That targeting underpins squamous cell carcinoma in humans, the team says. Deletion of GRHL3 in adult epidermis leads to a loss of expression in PTEN and, in turn, the development of aggressive squamous cell carcinoma. "Restoration of PTEN expression completely abrogates SCC formation," the authors write. "Reduced levels of GRHL3 and PTEN are evident in human skin, and head and neck SCC, associated with increased expression of miR-21, which targets both tumor suppressors."

Also in Cancer Cell this week, an international research team has found that the NOD-like receptor NLRP12 attenuates colon inflammation and tumorigenesis. The researchers analyzed NLRP12-deficient mice and found they are highly susceptible to colon inflammation and tumorigenesis. "Enhanced colon inflammation and colorectal tumor development in NLRP12-deficient mice are due to a failure to dampen NF-B and ERK activation in macrophages," the authors write. "These results reveal a critical role for NLRP12 in maintaining intestinal homeostasis and providing protection against colorectal tumorigenesis."

Finally in Cancer Cell this week, researchers in Canada write that the inhibition of mitochondrial translation could be used as a therapeutic strategy to treat human acute myeloid leukemia. The team performed a chemical screen on two human leukemia cell lines and found that the antimicrobial tygecycline selectively kills leukemia stem and progenitor cells while leaving normal cells alone. "ShRNA-mediated knockdown of EF-Tu mitochondrial translation factor in leukemic cells reproduced the antileukemia activity of tigecycline," the authors write. "These effects were derivative of mitochondrial biogenesis that, together with an increased basal oxygen consumption, proved to be enhanced in AML versus normal hematopoietic cells and were also important for their difference in tigecycline sensitivity."

The Scan

Lung Cancer Response to Checkpoint Inhibitors Reflected in Circulating Tumor DNA

In non-small cell lung cancer patients, researchers find in JCO Precision Oncology that survival benefits after immune checkpoint blockade coincide with a dip in ctDNA levels.

Study Reviews Family, Provider Responses to Rapid Whole-Genome Sequencing Follow-up

Investigators identified in the European Journal of Human Genetics variable follow-up practices after rapid whole-genome sequencing.

BMI-Related Variants Show Age-Related Stability in UK Biobank Participants

Researchers followed body mass index variant stability with genomic structural equation modeling and genome-wide association studies of 40- to 72-year olds in PLOS Genetics.

Genome Sequences Reveal Range Mutations in Induced Pluripotent Stem Cells

Researchers in Nature Genetics detect somatic mutation variation across iPSCs generated from blood or skin fibroblast cell sources, along with selection for BCOR gene mutations.