Actin assembly supplies the structural framework for cell morphology and migration. Beyond structure, this actin framework can also be engaged to drive biochemical signaling programs. Here, we describe how the hyperactivation of Rac1 via the P29S mutation (Rac1P29S) in melanoma hijacks branched actin network assembly to coordinate proliferative cues that facilitate metastasis and drug resistance. Upon growth challenge, Rac1P29S-harboring melanoma cells massively upregulate lamellipodia formation by dendritic actin polymerization. These extended lamellipodia form a signaling microdomain that sequesters and phospho-inactivates the tumor suppressor NF2/Merlin, driving Rac1P29S cell proliferation in growth suppressive conditions. These biochemically active lamellipodia require cell-substrate attachment but not focal adhesion assembly and drive proliferation independently of the ERK/MAPK pathway. These data suggest a critical link between cell morphology and cell signaling and reconcile the dichotomy of Rac1's regulation of both proliferation and actin assembly by revealing a mutual signaling axis wherein actin assembly drives proliferation in melanoma.
Pubmed ID: 31063759 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsSoftware package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsWeb application that helps design, evaluate and clone guide sequences for the CRISPR/Cas9 system. This sgRNA design tool assists with guide selection in a variety of genomes and pre-calculated results for all human coding exons as a UCSC Genome Browser track.
View all literature mentionsThis monoclonal targets ARPC1B
View all literature mentionsThis polyclonal targets ERK 1 (C-16)
View all literature mentionsThis monoclonal targets Arp3 (A-1)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets Human ARPC1A
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets RFP
View all literature mentionsThis monoclonal targets Phospho-Histone H3 (Ser10)
View all literature mentionsThis polyclonal targets NF2
View all literature mentionsThis monoclonal targets Merlin
View all literature mentionsThis polyclonal targets Phospho-Myosin Light Chain 2 (Thr18/Ser19)
View all literature mentionsThis monoclonal targets Myosin Light Chain 2
View all literature mentionsThis monoclonal targets RhoA (67B9) Rabbit mAb
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsThis monoclonal targets Talin
View all literature mentionsThis monoclonal targets Paxillin
View all literature mentionsThis monoclonal targets FAK
View all literature mentionsThis polyclonal targets Phospho-Paxillin (Tyr118)
View all literature mentionsThis monoclonal targets Human Phospho-Paxillin (Y31) MAb (Clone 698239)
View all literature mentionsThis monoclonal targets CCND1
View all literature mentionsThis unknown targets GAPDH
View all literature mentionsThis polyclonal targets MEK1/2
View all literature mentionsThis monoclonal targets Phospho-FAK (Tyr397) (D20B1) Rabbit mAb
View all literature mentionsThis monoclonal targets Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204) (E10) Mouse mAb
View all literature mentionsThis polyclonal targets Phospho-MEK1/2 (Ser217/221)
View all literature mentions
Mus musculus with name NOD.Cg-Prkdcscid Il2rg
Cell line IGR-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line A-375 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsAn online resource which helps researchers manage and organize labs and experimental results by supplying molecular biology software tools for experimental design and data analysis. Benchling provides tools for functions such as primer design and colony counting as well as CRISPR guide design and automated Gibson and Golden Gate cloning. Users can take notes in line with data, link data across entries, keep files and data in one place, and manage and keep track of team progress. An enterprise version of Benchling is available for scientists working within an organization with additional administrative, compliance, and security protocols.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsMulti paradigm numerical computing environment and fourth generation programming language developed by MathWorks. Allows matrix manipulations, plotting of functions and data, implementation of algorithms, creation of user interfaces, and interfacing with programs written in other languages, including C, C++, Java, Fortran and Python. Used to explore and visualize ideas and collaborate across disciplines including signal and image processing, communications, control systems, and computational finance.
View all literature mentionsTool for interactive image classification, segmentation and analysis, built as a modular software framework, which currently has workflows for automated (supervised) pixel- and object-level classification, automated and semi-automated object tracking, semi-automated segmentation and object counting without detection.
View all literature mentions