HDAC6 is required for invadopodia activity and invasion by breast tumor cells.
Invasion across tissue boundaries by metastatic tumor cells depends on the proteolytic degradation of the extracellular matrix, initiated by the formation of invadopodia, actin-driven membrane protrusions with matrix-degradative activity. Yet, mechanisms underlying invadopodia formation remain largely unknown. In this report, we examined the role of the histone deacetylase HDAC6 in invadopodia formation and invasion by breast cancer cells. Using small interfering RNA silencing of protein expression in highly invasive MDA-MB-231 breast adenocarcinoma cells, we show that HDAC6 is required for two-dimensional matrix proteolysis. In addition, we demonstrate that HDAC6 acts as a tubulin and cortactin deacetylase. We also report that the inhibition of HDAC6 by siRNA or treatment with HDAC inhibitor TSA results in a decreased invasion capacity of a three-dimensional type I collagen matrix by MDA-MB-231 cells. These data identify HDAC6 as a critical component of the invasive apparatus of tumor cells, in both two- and three-dimensional matrices.
Rey
Mercedes
M
Institut Curie, Research Center, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
Irondelle
Marie
M
Waharte
François
F
Lizarraga
Floria
F
Chavrier
Philippe
P
D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology* / Q000648:ultrastructure; D001485:Basement Membrane / Q000201:enzymology / Q000473:pathology; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology* / Q000648:ultrastructure; D045744:Cell Line, Tumor; D022081:Cell Surface Extensions / Q000201:enzymology* / Q000473:pathology; D024042:Collagen Type I / Q000378:metabolism; D051356:Cortactin / Q000378:metabolism; D005109:Extracellular Matrix / Q000201:enzymology / Q000473:pathology; D005260:Female; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D014162:Transfection
D024042:Collagen Type I; D051356:Cortactin; D034741:RNA, Small Interfering; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases