Search

Invadopodia are extracellular matrix (ECM) degrading structures, which promote cancer cell invasion. The nucleus is increasingly viewed as a mechanosensory organelle that determines migratory strategies. However, how the nucleus crosstalks with invadopodia is little known. Here, we report that the oncogenic septin 9 isoform 1 (SEPT9_i1) is a component of breast cancer invadopodia. SEPT9_i1 depletion diminishes invadopodium formation and the clustering of the invadopodium precursor components TKS5 and cortactin. This phenotype is characterized by deformed nuclei and nuclear envelopes with folds and grooves. We show that SEPT9_i1 localizes to the nuclear envelope and juxtanuclear invadopodia. Moreover, exogenous lamin A rescues nuclear morphology and juxtanuclear TKS5 clusters. Importantly, SEPT9_i1 is required for the amplification of juxtanuclear invadopodia, which is induced by the epidermal growth factor. We posit that nuclei of low deformability favor the formation of juxtanuclear invadopodia in a SEPT9_i1-dependent manner, which functions as a tunable mechanism for overcoming ECM impenetrability. [Display omitted] • The oncogenic SEPT9_i1 is enriched in breast cancer invadopodia in 2D and 3D ECM • SEPT9_i1 promotes invadopodium precursor clustering and invadopodium elongation • SEPT9_i1 localizes to the nuclear envelope and reduces nuclear deformability • SEPT9_i1 is required for EGF-induced amplification of juxtanuclear invadopodia Invadopodia promote the invasion of metastatic cancers. The nucleus is a mechanosensory organelle that determines migratory strategies, but how it crosstalks with invadopodia is unknown. Okletey et al. show that the oncogenic isoform SEPT9_i1 promotes nuclear envelope stability and the formation of invadopodia at juxtanuclear areas of the plasma membrane. [ABSTRACT FROM AUTHOR]