CD147: a small molecule transporter ancillary protein at the crossroad of multiple hallmarks of cancer and metabolic reprogramming

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...

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Bibliographic Details
Published in:Oncotarget 2017-01, Vol.8 (4), p.6742-6762
Main Authors: Kendrick, Agnieszka A, Schafer, Johnathon, Dzieciatkowska, Monika, Nemkov, Travis, D'Alessandro, Angelo, Neelakantan, Deepika, Ford, Heide L, Pearson, Chad G, Weekes, Colin D, Hansen, Kirk C, Eisenmesser, Elan Z
Format: Article
Language:English
Subjects:
Amino Acids - metabolism
Animals
Basigin - genetics
Basigin - metabolism
Calcium Signaling
Cell Adhesion
Cell Line, Tumor
Cell Movement
Cell Proliferation
Cellular Reprogramming
Energy Metabolism
Female
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Humans
Membrane Transport Proteins - genetics
Membrane Transport Proteins - metabolism
Mice, Nude
Monocarboxylic Acid Transporters - genetics
Monocarboxylic Acid Transporters - metabolism
Pancreatic Neoplasms - genetics
Pancreatic Neoplasms - metabolism
Pancreatic Neoplasms - pathology
Plasma Membrane Calcium-Transporting ATPases - genetics
Plasma Membrane Calcium-Transporting ATPases - metabolism
Proteasome Endopeptidase Complex - metabolism
Protein Binding
Proteolysis
Research Paper
RNA Interference
Time Factors
Transfection
Tumor Burden
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Summary: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.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.14272