Loss of expression of the recycling receptor, FcRn, promotes tumor cell growth by increasing albumin consumption
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Rafal Swiercz1,2,*, Min Mo1,2,*, Priyanka Khare1,2, Zita Schneider1,2, Raimund J. Ober1,3, Elizabeth Sally Ward1,2
1Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, College Station, TX 77843, USA
2Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77807, USA
3Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843, USA
*These authors have contributed equally to this work
Elizabeth Sally Ward, email: firstname.lastname@example.org
Keywords: neonatal Fc receptor (FcRn), albumin, tumor suppressor, recycling receptor, hypoalbuminemia
Received: August 25, 2016 Accepted: October 27, 2016 Published: December 10, 2016
Tumor cells rely on high concentrations of amino acids to support their growth and proliferation. Although increased macropinocytic uptake and lysosomal degradation of the most abundant serum protein, albumin, in Ras-transformed cells can meet these demands, it is not understood how the majority of tumor cells that express wild type Ras achieve this. In the current study we reveal that the neonatal Fc receptor, FcRn, regulates tumor cell proliferation through the ability to recycle its ligand, albumin. By contrast with normal epithelial cells, we show that human FcRn is present at very low or undetectable levels in the majority of tumor cell lines analyzed. Remarkably, shRNA-mediated ablation of FcRn expression in an FcRn-positive tumor cell line results in a substantial growth increase of tumor xenografts, whereas enforced expression of this receptor by lentiviral transduction has the reverse effect. Moreover, intracellular albumin and glutamate levels are increased by the loss of FcRn-mediated recycling of albumin, combined with hypoalbuminemia in tumor-bearing mice. These studies identify a novel role for FcRn as a suppressor of tumor growth and have implications for the use of this receptor as a prognostic indicator and therapeutic target.
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