title: CD147: a small molecule transporter ancillary protein at the crossroad of multiple hallmarks of cancer and metabolic reprogramming.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, CO, USA.
authors.forename: Agnieszka A
authors.initials: AA
authors.lastname: Kendrick
authors.affiliation: Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, CO, USA.
authors.forename: Johnathon
authors.initials: J
authors.lastname: Schafer
authors.affiliation: Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, CO, USA.
authors.forename: Monika
authors.initials: M
authors.lastname: Dzieciatkowska
authors.affiliation: Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, CO, USA.
authors.forename: Travis
authors.initials: T
authors.lastname: Nemkov
authors.affiliation: Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, CO, USA.
authors.forename: Angelo
authors.initials: A
authors.lastname: D'Alessandro
authors.affiliation: Department of Pharmacology, School of Medicine, University of Colorado Denver, CO, USA.
authors.forename: Deepika
authors.initials: D
authors.lastname: Neelakantan
authors.affiliation: Department of Pharmacology, School of Medicine, University of Colorado Denver, CO, USA.
authors.forename: Heide L
authors.initials: HL
authors.lastname: Ford
authors.affiliation: Department of Cell and Developmental Biology, School of Medicine, University of Colorado Denver, CO, USA.
authors.forename: Chad G
authors.initials: CG
authors.lastname: Pearson
authors.affiliation: Division of Oncology, Department of Medicine, University of Colorado Denver, CO, USA.
authors.forename: Colin D
authors.initials: CD
authors.lastname: Weekes
authors.affiliation: Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, CO, USA.
authors.forename: Kirk C
authors.initials: KC
authors.lastname: Hansen
authors.affiliation: Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, CO, USA.
authors.forename: Elan Z
authors.initials: EZ
authors.lastname: Eisenmesser
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D051926:Basigin / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D065150:Cellular Reprogramming; D004734:Energy Metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D008819:Mice, Nude; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D059748:Proteolysis; D034622:RNA Interference; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden
chemical_list: C506952:ATP2B1 protein, human; D000596:Amino Acids; C497886:BSG protein, human; D026901:Membrane Transport Proteins; D027501:Monocarboxylic Acid Transporters; D051926:Basigin; D046988:Proteasome Endopeptidase Complex; D053499:Plasma Membrane Calcium-Transporting ATPases
keywords: PDAC; ancillary protein; metabolism; transmembrane; tumor microenvironment