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An oncogenic isoform of septin 9 promotes the formation of juxtanuclear invadopodia by reducing nuclear deformability
Journal article   Open access   Peer reviewed

An oncogenic isoform of septin 9 promotes the formation of juxtanuclear invadopodia by reducing nuclear deformability

Joshua Okletey, Dimitrios Angelis, Tia M. Jones, Cristina Montagna and Elias T. Spiliotis
Cell reports (Cambridge), v 42(8), 112893
29 Aug 2023
DOI: https://doi.org/10.1016/j.celrep.2023.112893
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1016/j.celrep.2023.112893View
Published, Version of Record (VoR)CC BY-NC-ND V4.0,  Open

Abstract

cancer metastasis epidermal growth factor extracellular matrix invadopodia invadopodium precursor nuclear envelope nuclear fold nuclear groove nucleus septins
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.

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Collaboration types
Domestic collaboration
Web of Science research areas
Cell Biology
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