FiloQuant reveals increased filopodia density during breast cancer progression

Jacquemet, Guillaume; Paatero, Ilkka; Carisey, Alexandre F.; Padzik, Artur; Orange, Jordan S.; Hamidi, Hellyeh; Ivaska, Johanna

doi:10.1083/jcb.201704045

Cited by 126 publications

(126 citation statements)

References 41 publications

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“…Imaging was performed by Nokia A1 Plus (Nikon, Melville, NY). Analyses were performed using the OrientationJ and FiloQuantImageJ plugins (Jacquemet et al, 2017).…”

Section: Methodsmentioning

confidence: 99%

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Low‐intensity pulsed ultrasound affects growth, differentiation, migration, and epithelial‐to‐mesenchymal transition of colorectal cancer cells

Lucchetti

Perelli

Colella

et al. 2020

Journal Cellular Physiology

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Ultrasound (US) offers potentially important opportunities from a therapeutic point of view. Thus, the study of the biological effects of US on cancer cells is important to understand the consequences of these changes on the malignant phenotype. This study aimed to investigate the effects of low‐intensity ultrasound (LIPUS) on the phenotype of colorectal cancer cell lines. Cell proliferation was evaluated by viability test and by evaluation of pERK expression, while cell motility using the scratch test. Cell differentiation was evaluated assessing alkaline phosphatase activity. Epithelial mesenchymal transition was assessed by analyzing the expression of Vimentin and E‐Cadherin. Release and uptake of extracellular vesicles (EVs) were evaluated by flow cytometry. LIPUS effects on the organization of cytoskeleton were analyzed by confocal microscopy and by evaluation of Rho GTPase expression. No alterations in vitality and clonogenicity were observed when the intermediate (0.4 MPa) and the lowest (0.035 MPa) acoustic intensities were administered while the treatment with high intensity (1 MPa) induced a reduction of both cell viability and clonogenicity in both cell lines in a frequency‐dependent manner. LIPUS promoted the differentiation of colon cancer cells, affected epithelial‐to‐mesenchymal transition, promoted the closure of a wound as well as increased the release of EVs compared with untreated cells. LIPUS‐induced increase in cell motility was likely due to a Rho GTPase‐dependent mechanism. Overall, the results obtained warrant further studies on the potential combined effect of LIPUS with differentiating agents and on their potential use in a clinical setting.

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“…Imaging was performed by Nokia A1 Plus (Nikon, Melville, NY). Analyses were performed using the OrientationJ and FiloQuantImageJ plugins (Jacquemet et al, 2017).…”

Section: Methodsmentioning

confidence: 99%

“…Analyses were performed using the OrientationJ and FiloQuantIma-geJ plugins (Jacquemet et al, 2017).…”

Section: Confocal Microscopymentioning

confidence: 99%

Low‐intensity pulsed ultrasound affects growth, differentiation, migration, and epithelial‐to‐mesenchymal transition of colorectal cancer cells

Lucchetti

Perelli

Colella

et al. 2020

Journal Cellular Physiology

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“…Cell motility through complex 3D microenvironments also requires efficient probing of the cell surroundings via specialized sensory protrusions such as filopodia (Jacquemet et al, 2015). Filopodia are finger-like actin-rich protrusions widely used by cells in vivo during normal processes, such as development (Sato et al, 2017;Haas and Gilmour, 2006;Zhang et al, 2018), angiogenesis (Gerhardt et al, 2003), immune surveillance (Liu et al, 2018), and wound healing (Wood et al, 2002;Pickering et al, 2013), and also during tumourigenesis (Shibue et al, 2012(Shibue et al, , 2013 and cancer cell dissemination (Paul et al, 2015;Jacquemet et al, 2017;Follain et al, 2018;Liu et al, 2018). Filopodia have integrin-positive adhesive tips for ECM sensing and cells can employ filopodia to recognize ECM gradients (Johnson et al, 2015), ECM topography (Albuschies and Vogel, 2013) or ECM stiffness (Wong et al, 2014;Chan and Odde, 2008).…”

Section: Introductionmentioning

confidence: 99%

Filopodome mapping identifies p130Cas as a mechanosensitive regulator of filopodia stability

Jacquemet

Saup

Hamidi

et al. 2018

Preprint

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Filopodia are adhesive cellular protrusions specialised in the detection of extracellular matrix (ECM)-derived cues. While ECM engagement at focal adhesions is known to trigger the recruitment of hundreds of proteins ("adhesome") to fine-tune cellular behaviour, the components of the filopodia adhesions remain undefined. Here, we performed a structured illumination microscopy-based screen to map the localisation of 80 target proteins, linked to cell adhesion and migration, within filopodia. We demonstrate preferential enrichment of several adhesion proteins to either filopodia tips, filopodia shafts, or shaft subdomains suggesting divergent, spatially restricted functions for these proteins. Moreover, proteins with phosphoinositide (PI) binding sites are particularly enriched in filopodia. This, together with the strong localisation of PI(3,4)P 2 in filopodia tips, predicts critical roles for PIs in regulating filopodia ultra-structure and function. Our mapping further reveals that filopodia adhesions consist of a unique set of proteins, the filopodome, that are distinct from classical nascent adhesions, focal adhesions and fibrillar adhesions. Using live imaging, we observe that filopodia adhesions can give rise to nascent adhesions, which, in turn, form focal adhesions. Finally, we demonstrate that p130Cas (BCAR1) is recruited to filopodia tips via its CCHD domain and acts as a mechanosensitive regulator of filopodia stability. Filopodia | Cell adhesions | SIM | p130Cas

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“…Filpodial and lammelipodial protrusions are present at the invasive front of cancer cells in vitro, and in in vivo tumor spheroid models, but their morphology -particularly in in vivo tumor tissue is less studied [10,35], We used light and electron (SEM/FIB-SEM) microscopy to examine protrusion organization in in vitro cell models and asked if this organization was similar in in vivo breast tumor tissue.…”

Section: Segregated Distant Morphology Of Breast Cancer Filopodia Anmentioning

confidence: 99%

HER2 Cancer Protrusion Growth Signaling Regulated by Unhindered, Localized Filopodial Dynamics

Lam

Wang

Mostofian

et al. 2019

Preprint

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Protrusions are plasma membrane extensions that are found in almost every cell in the human body. Cancer cell filopodial and lamellipodial protrusions play key roles in the integral processes of cell motility and signaling underlying tumor invasion and metastasis. HER2 (ErbB-2) is overexpressed in diverse types of tumors and regulates PI3K-pathway-mediated protrusion growth. It is known that HER2 resides at breast cancer cell protrusions, but how protrusion-based HER2 spatiotemporal dynamics shape cancer signaling is unclear. Here, we study how HER2 location and motion regulate protrusion signaling and growth using quantitative spatio-temporal molecular imaging approaches. Our data highlight morphologically-segregated features of filopodial and lamellipodial protrusions, in in vitro 2D breast cancer cells and in vivo intact breast tumor. Functionalsegregation parallels morphological-segregation, as HER2 and its activated downstream pAKT-PI3K signaling remain spatiallylocalized at protrusions, provoking new protrusion growth proximal to sites of HER2 activation. HER2 in SKBR3 breast cancer cell filopodia exhibits fast, linearly-directed motion that is distinct from lamellipodia and non-protrusion subcellular regions (~3-4 times greater diffusion constant, rapid speeds of 2-3 um 2 /s). Surprisingly, filopodial HER2 motion is passive, requiring no active energy sources. Moreover, while HER2 motion in lamellipodia and non-protrusion regions show hindered diffusion typical of membrane proteins, HER2 diffuses freely within filopodia. We conclude that HER2 activation, propagation, and functional protrusion growth is a local process in which filopodia have evolved to exploit Brownian thermal fluctuations within a barrier-free nanostructure to transduce rapid signaling. These results support the importance of developing filopodia and other protrusion-targeted strategies for cancer.

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FiloQuant reveals increased filopodia density during breast cancer progression

Cited by 126 publications

References 41 publications

Low‐intensity pulsed ultrasound affects growth, differentiation, migration, and epithelial‐to‐mesenchymal transition of colorectal cancer cells

Low‐intensity pulsed ultrasound affects growth, differentiation, migration, and epithelial‐to‐mesenchymal transition of colorectal cancer cells

Filopodome mapping identifies p130Cas as a mechanosensitive regulator of filopodia stability

HER2 Cancer Protrusion Growth Signaling Regulated by Unhindered, Localized Filopodial Dynamics

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