Knock out of the BASIGIN/CD147 chaperone of lactate/H+ symporters disproves its pro-tumour action via extracellular matrix metalloproteases (MMPs) induction.
BASIGIN/CD147/EMMPRIN is a multifunctional transmembrane glycoprotein strongly expressed in tumours. BASIGIN controls tumour metabolism, particularly glycolysis by facilitating lactic acid export through the two monocarboxylate transporters MCT1 and hypoxia-inducible MCT4. However, before being recognized as a co-carrier of MCTs, BASIGIN was described as an inducer of extracellular matrix metalloproteases (MMPs). Early on, a model emerged in which, tumour cells use the extracellular domain of BASIGIN to recognize and stimulate neighbouring fibroblasts to produce MMPs. However, this model has remained hypothetical since a direct link between BASIGIN and MMPs production has not yet been clearly established. To validate the BASIGIN/MMP hypothesis, we developed BASIGIN knockouts in three human tumour cell lines derived from glioma, colon, and lung adenocarcinoma. By using co-culture experiments of either human or mouse fibroblasts and tumour cell lines we showed, contrary to what has been abundantly published, that the disruption of BASIGIN in tumour cells and in MEFs has no action on the production of MMPs. Our findings do not support the notion that the pro-tumoural action of BASIGIN is mediated via induction of MMPs. Therefore, we propose that to date, the strongest pro-tumoural action of BASIGIN is mediated through the control of fermentative glycolysis.
INSERM, CNRS, Institute for Research on Cancer and Aging, Nice (IRCAN), University of Nice Sophia Antipolis, Centre Antoine Lacassagne, Nice, France.
Ibtissam
I
Marchiq
INSERM, CNRS, Institute for Research on Cancer and Aging, Nice (IRCAN), University of Nice Sophia Antipolis, Medical School, Nice, France.
Jean
J
Albrengues
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus of Gualtar, Braga, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Braga, Guimarães, Portugal.
Sara
S
Granja
INSERM, CNRS, Institute for Research on Cancer and Aging, Nice (IRCAN), University of Nice Sophia Antipolis, Medical School, Nice, France.
Cédric
C
Gaggioli
INSERM, CNRS, Institute for Research on Cancer and Aging, Nice (IRCAN), University of Nice Sophia Antipolis, Centre Antoine Lacassagne, Nice, France.|Centre Scientifique de Monaco (CSM), Quai Antoine Ier MC, France.
Jacques
J
Pouysségur
INSERM, CNRS, Institute for Research on Cancer and Aging, Nice (IRCAN), University of Nice Sophia Antipolis, Centre Antoine Lacassagne, Nice, France.
Marie-Pierre
MP
Simon
D000818:Animals; D051926:Basigin / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D015536:Down-Regulation; D004720:Endonucleases / Q000378:metabolism; D005347:Fibroblasts / Q000201:enzymology*; D015972:Gene Expression Regulation, Neoplastic; D055786:Gene Knockout Techniques; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism*; D019899:Paracrine Communication; D015398:Signal Transduction; D027981:Symporters / Q000378:metabolism*; D014162:Transfection; D016335:Zinc Fingers; D000099233:Monocarboxylate Transport Protein 1
D051926:Basigin; D017077:Culture Media, Conditioned; D004720:Endonucleases; D020782:Matrix Metalloproteinases; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C497886:BSG protein, human; C497887:Bsg protein, mouse; C406962:SLC16A4 protein, human
MCT; cancer biology; glycolysis; lactic acid; membrane transport