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The interactome of metabolic enzyme carbonic anhydrase IX reveals novel roles in tumor cell migration and invadopodia/MMP14-mediated invasion

Swayampakula, M ; McDonald, P C ; Vallejo, M ; Coyaud, E ; Chafe, S C ; Westerback, A ; Venkateswaran, G ; Shankar, J ; Gao, G ; Laurent, E M N ; Lou, Y ; Bennewith, K L ; Supuran, C T ; Nabi, I R ; Raught, B ; Dedhar, S

Oncogene, 2017-11, Vol.36 (45), p.6244-6261 [Periódico revisado por pares]

England: Nature Publishing Group

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The interactome of metabolic enzyme carbonic anhydrase IX reveals novel roles in tumor cell migration and invadopodia/MMP14-mediated invasion
Autor: Swayampakula, M ; McDonald, P C ; Vallejo, M ; Coyaud, E ; Chafe, S C ; Westerback, A ; Venkateswaran, G ; Shankar, J ; Gao, G ; Laurent, E M N ; Lou, Y ; Bennewith, K L ; Supuran, C T ; Nabi, I R ; Raught, B ; Dedhar, S
Assuntos: Actin ; Animals ; Antigens, Neoplasm - genetics ; Antigens, Neoplasm - metabolism ; Biotinylation ; Breast cancer ; Breast Neoplasms - enzymology ; Breast Neoplasms - genetics ; Breast Neoplasms - pathology ; Carbonic anhydrase ; Carbonic Anhydrase IX - genetics ; Carbonic Anhydrase IX - metabolism ; Carbonic anhydrases ; Care and treatment ; Cell adhesion & migration ; Cell Line, Tumor ; Cell migration ; Cell Movement - physiology ; Cell surface ; Cofilin ; Collagen ; Development and progression ; Enzymes ; Female ; Genetic aspects ; Health aspects ; HEK293 Cells ; Humans ; Hypoxia ; Immunofluorescence ; Integrins ; Lamellipodia ; Mammary Neoplasms, Experimental - enzymology ; Mammary Neoplasms, Experimental - genetics ; Mammary Neoplasms, Experimental - pathology ; Matrix metalloproteinase ; Matrix Metalloproteinase 14 - genetics ; Matrix Metalloproteinase 14 - metabolism ; MCF-7 Cells ; Metabolism ; Metalloproteinase ; Mice ; Original ; pH effects ; Phosphorylation ; Podosomes - enzymology ; Podosomes - genetics ; Podosomes - pathology ; Pseudopodia ; Transcription factors ; Transfection ; Tumors
É parte de: Oncogene, 2017-11, Vol.36 (45), p.6244-6261
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SourceType-Scholarly Journals-1
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These authors contributed equally to this work.
Descrição: Carbonic anhydrase IX (CAIX) is a hypoxia inducible factor 1-induced, cell surface pH regulating enzyme with an established role in tumor progression and clinical outcome. However, the molecular basis of CAIX-mediated tumor progression remains unclear. Here, we have utilized proximity dependent biotinylation (BioID) to map the CAIX 'interactome' in breast cancer cells in order to identify physiologically relevant CAIX-associating proteins with potential roles in tumor progression. High confidence proteins identified include metabolic transporters, β1 integrins, integrin-associated protein CD98hc and matrix metalloprotease 14 (MMP14). Biochemical studies validate the association of CAIX with α2β1 integrin, CD98hc and MMP14, and immunofluorescence microscopy demonstrates colocalization of CAIX with α2β1 integrin and MMP14 in F-actin/cofilin-positive lamellipodia/pseudopodia, and with MMP14 to cortactin/Tks5-positive invadopodia. Modulation of CAIX expression and activity results in significant changes in cell migration, collagen degradation and invasion. Mechanistically, we demonstrate that CAIX associates with MMP14 through potential phosphorylation residues within its intracellular domain, and that CAIX enhances MMP14-mediated collagen degradation by directly contributing hydrogen ions required for MMP14 catalytic activity. These findings establish hypoxia-induced CAIX as a novel metabolic component of cellular migration and invasion structures, and provide new mechanistic insights into its role in tumor cell biology.
Editor: England: Nature Publishing Group
Idioma: Inglês

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The interactome of metabolic enzyme carbonic anhydrase IX reveals novel roles in tumor cell migration and invadopodia/MMP14-mediated invasion

Swayampakula, M ; McDonald, P C ; Vallejo, M ; Coyaud, E ; Chafe, S C ; Westerback, A ; Venkateswaran, G ; Shankar, J ; Gao, G ; Laurent, E M N ; Lou, Y ; Bennewith, K L ; Supuran, C T ; Nabi, I R ; Raught, B ; Dedhar, S

England: Nature Publishing Group

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