CD147: a small molecule transporter ancillary protein at the crossroad of multiple hallmarks of cancer and metabolic reprogramming
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Agnieszka A. Kendrick1, Johnathon Schafer1, Monika Dzieciatkowska1, Travis Nemkov1, Angelo D’Alessandro1, Deepika Neelakantan2, Heide L. Ford2, Chad G. Pearson3, Colin D. Weekes4, Kirk C. Hansen1, Elan Z. Eisenmesser1
1Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, CO, USA
2Department of Pharmacology, School of Medicine, University of Colorado Denver, CO, USA
3Department of Cell and Developmental Biology, School of Medicine, University of Colorado Denver, CO, USA
4Division of Oncology, Department of Medicine, University of Colorado Denver, CO, USA
Elan Z. Eisenmesser, email: email@example.com
Keywords: metabolism, ancillary protein, PDAC, transmembrane, tumor microenvironment
Received: September 20, 2016 Accepted: November 30, 2016 Published: December 27, 2016
Increased expression of CD147 in pancreatic cancer has been proposed to play a critical role in cancer progression via CD147 chaperone function for lactate monocarboxylate transporters (MCTs). Here, we show for the first time that CD147 interacts with membrane transporters beyond MCTs and exhibits a protective role for several of its interacting partners. CD147 prevents its interacting partner’s proteasome-dependent degradation and incorrect plasma membrane localization through the CD147 transmembrane (TM) region. The interactions with transmembrane small molecule and ion transporters identified here indicate a central role of CD147 in pancreatic cancer metabolic reprogramming, particularly with respect to amino acid anabolism and calcium signaling. Importantly, CD147 genetic ablation prevents pancreatic cancer cell proliferation and tumor growth in vitro and in vivo in conjunction with metabolic rewiring towards amino acid anabolism, thus paving the way for future combined pharmacological treatments.
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