Public Release:  JCI early table of contents for Dec. 9, 2013

Journal of Clinical Investigation

Breast cancer prognosis associated with oncometabolite accumulation

The metabolic profile of cancer cells can be used to develop therapies and identify biomarkers associated with cancer outcome. In this issue of the Journal of Clinical Investigation Stefan Ambs and colleagues at the National Cancer Institute discovered an association between the oncometabolite 2-hydroxyglutarate (2-HG) levels, DNA methylation patterns, and breast cancer prognosis. The authors identified a breast cancer subtype with high levels of 2-HG, and a district DNA methylation pattern that was associated with reduced survival. This breast cancer subtype was common in African-American breast cancer patients, who as a group have a high prevalence of aggressive breast cancers. This study indicates that evaluation of 2-HG along with DNA methylation may be a useful biomarker for breast cancer diagnosis and prognosis

TITLE: MYC-driven accumulation of 2-hydroxyglutarate is associated with breast cancer prognosis

National Cancer Institute, Bethesda, MD, USA
Phone: 301-496-4668; E-mail:

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Choloroquine reduces formation of bone resorbing cells in murine osteoporosis

Bone homeostasis requires precise balance between deposition of new bone by osteoblasts and resorption of old bone by osteoclasts. Bone diseases, including osteoporosis and rheumatoid arthritis, are the result of increased osteoclast activity and formation, which allows bone resorption to outpace deposition. In this issue of the Journal of Clinical Investigation, Brendan Boyce and colleagues at the University of Rochester evaluated the role of TNF receptor-associated receptor 3 (TRAF3) in promoting osteoclast formation. Mice lacking TRAF3 in osteoclast precursor cells had mild osteoporosis that was associated with increased osteoclast formation. The authors found that chloroquine treatment increased TRAF3 in osteoclast precursor cells and limited osteoclast generation. Furthermore, treatment of mouse models of osteoporosis with chloroquine inhibited osteoclast formation. These studies implicate that therapies aimed at increasing TRAF3 in osteoclast precursor cells may limit bone loss for those with bone diseases.

TITLE: Chloroquine reduces osteoclastogenesis in murine osteoporosis by preventing TRAF3 degradation

University of Rochester Medical Center, Rochester, NY, USA
Phone: 585-275-5837; Fax: 585-276-2832; E-mail:

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Increased sugar uptake promotes oncogenesis via EPAC/RAP1 and O-GlcNAc pathways


Mina Bissell

Lawrence Berkeley National Laboratory, Berkeley, CA, USA

Phone: 510 486-4365; E-mail:

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TITLE: Hematopoietic stem cells are acutely sensitive to Acd shelterin gene inactivation

University of Michigan, Ann Arbor, MI, USA
Phone: 734-763-3599; Fax: 734-615-5493; E-mail:

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TITLE: Embryonic exposure to excess thyroid hormone causes thyrotrope cell death

AUTHOR CONTACT: Ksenia Tonyushkina
Baystate Medical Center, Springfield, MA, USA
Phone: 413-794-3510; E-mail:

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TITLE: Diverting T helper cell trafficking through increased plasticity attenuates autoimmune encephalomyelitis

Albany Medical College, Albany, NY, USA
Phone: 518-262-6731; E-mail:

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TITLE: Combined SFK/MEK inhibition prevents metastatic outgrowth of dormant tumor cells

National Cancer Institute, Potomac, MD, USA
Phone: 301-435-5193; Fax: 301-496-8709; E-mail:

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TITLE: LRIG1 inhibits STAT3-dependent inflammation to maintain corneal homeostasis

AUTHOR CONTACT: Takahiro Nakamura
Kyoto Prefectural University of Medicine, Kyoto, , JPN
Phone: +81-75-251-5578; Fax: +81-75-251-5663; E-mail:

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