Cortactin recruits FMNL2 to promote actin polymerization and endosome motility in invadopodia formation

Ren, Xiaohu; Qiao, Yudan; Li, J.Y.; Li, X.M.; Zhang, Dingwen; Zhang, X.J.; Zhu, Xiongjie; Zhou, Weijun; Shi, Junpeng; Wang, W.; Liao, Wangjun; Ding, Yi; Li, Liang

doi:10.1016/j.canlet.2018.01.023

Cited by 31 publications

(20 citation statements)

References 41 publications

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“…The activity of Rho family GTPase is recognized as a convergent and common pathway from different inputs and an essential regulator of actin dynamics at invadopodia in each specific step. While Cdc42 alone or in cooperation with Rac1 participates only during the precursor assembly ( Nakahara et al, 2003 ; Yamaguchi et al, 2005 ; Ayala et al, 2009 ; Di Martino et al, 2014 ; Lin et al, 2014 ; Kedziora et al, 2016 ; Ren et al, 2018 ), RhoA alone or in cooperation with Cdc42 is specifically involved in invadopodia maturation ( Sakurai-Yageta et al, 2008 ; Hoshino et al, 2009 ; Daubon et al, 2012 ; Hwang et al, 2016 ; Yan et al, 2018 ). More recently, RhoC is emerging as a crucial coordinator of cofilin-dependent actin polymerization to the core of invadopodia, associated with focused ECM degradation and cell invasion ( Bravo-Cordero et al, 2011 ; Pignatelli et al, 2012 ; Semprucci et al, 2016 ; Di Modugno et al, 2018 ).…”

Section: General Features Of Invadopodiamentioning

confidence: 99%

Tumor Cellular and Microenvironmental Cues Controlling Invadopodia Formation

Masi

Caprara

Bagnato

et al. 2020

Front. Cell Dev. Biol.

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During the metastatic progression, invading cells might achieve degradation and subsequent invasion into the extracellular matrix (ECM) and the underlying vasculature using invadopodia, F-actin-based and force-supporting protrusive membrane structures, operating focalized proteolysis. Their formation is a dynamic process requiring the combined and synergistic activity of ECM-modifying proteins with cellular receptors, and the interplay with factors from the tumor microenvironment (TME). Significant advances have been made in understanding how invadopodia are assembled and how they progress in degradative protrusions, as well as their disassembly, and the cooperation between cellular signals and ECM conditions governing invadopodia formation and activity, holding promise to translation into the identification of molecular targets for therapeutic interventions. These findings have revealed the existence of biochemical and mechanical interactions not only between the actin cores of invadopodia and specific intracellular structures, including the cell nucleus, the microtubular network, and vesicular trafficking players, but also with elements of the TME, such as stromal cells, ECM components, mechanical forces, and metabolic conditions. These interactions reflect the complexity and intricate regulation of invadopodia and suggest that many aspects of their formation and function remain to be determined. In this review, we will provide a brief description of invadopodia and tackle the most recent findings on their regulation by cellular signaling as well as by inputs from the TME. The identification and interplay between these inputs will offer a deeper mechanistic understanding of cell invasion during the metastatic process and will help the development of more effective therapeutic strategies.

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Section: General Features Of Invadopodiamentioning

confidence: 99%

Tumor Cellular and Microenvironmental Cues Controlling Invadopodia Formation

Masi

Caprara

Bagnato

et al. 2020

Front. Cell Dev. Biol.

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“…In contrast, inhibition of Arp2/3 complex activation alone had no direct effect on filopodia length, pointing to the possibility that cortactin utilizes other binding partners to control filopodia length (Figure 7G). Considering that filopodia elongation is governed mainly by actin regulators at the plus end of actin bundles, phosphorylated cortactin may recruit formin to promote actin polymerization, as shown recently in invadopodia formation (Ren et al , 2018).…”

Section: Discussionmentioning

confidence: 78%

A single tyrosine phosphorylation site in cortactin is important for filopodia formation in neuronal growth cones

Ren

Brown

et al. 2019

MBoC

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Cortactin is a Src tyrosine phosphorylation substrate that regulates multiple actin-related cellular processes. While frequently studied in nonneuronal cells, the functions of cortactin in neuronal growth cones are not well understood. We recently reported that cortactin mediates the effects of Src tyrosine kinase in regulating actin organization and dynamics in both lamellipodia and filopodia of Aplysia growth cones. Here, we identified a single cortactin tyrosine phosphorylation site (Y499) to be important for the formation of filopodia. Overexpression of a 499F phospho-deficient cortactin mutant decreased filopodia length and density, whereas overexpression of a 499E phospho-mimetic mutant increased filopodia length. Using an antibody against cortactin pY499, we showed that tyrosine-phosphorylated cortactin is enriched along the leading edge. The leading edge localization of phosphorylated cortactin is Src2-dependent, F-actin–independent, and important for filopodia formation. In vitro kinase assays revealed that Src2 phosphorylates cortactin at Y499, although Y505 is the preferred site in vitro. Finally, we provide evidence that Arp2/3 complex acts downstream of phosphorylated cortactin to regulate density but not length of filopodia. In conclusion, we have characterized a tyrosine phosphorylation site in Aplysia cortactin that plays a major role in the Src/cortactin/Arp2/3 signaling pathway controlling filopodia formation.

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“…Invadopodia formation requires numerous proteins (65,66). Cortactin is an actin-binding protein that is closely associated with invadopodia through its interaction with other proteins (67). Cortactin is key for invadopodia formation and interacts with various proteins, such as Arp2/3, N-WASP, and F-actin (7,65,68).…”

Section: Role Of Cortactin In Invadopodia Formation and Functionmentioning

confidence: 99%

“…Invadopodium is a convergence point for a number of signals that regulate tumor cell behaviors, particularly systemic dissemination and metastasis ( 13 ). Cortactin is the switch that mediates invadopodia formation ( 54 , 55 , 67 , 74 , 75 , 80 ). It is regulated by numerous signaling pathways and factors, including the FAK pathway ( 81 ), Src ( 82 ), NF-κB ( 54 , 55 ), and other pathways that are closely associated with tumor metastasis ( 54 , 55 , 74 , 75 , 80 ).…”

Section: Potential Diosgenin-cortactin-invadopodia Mechanismmentioning

confidence: 99%

Inhibition of invadopodia formation by diosgenin in tumor cells (Review)

Lian

Meng

et al. 2020

Oncol Lett

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Diosgenin is a type of steroid extracted from the rhizome of Dioscorea plants. In traditional Chinese medicine, Dioscorea has the effect of 'eliminating phlegm, promoting digestion, relaxing tendons, promoting blood circulation and inhibiting malaria'. Recent studies have confirmed that diosgenin exhibits a number of pharmacological effects, including antitumor activities. Through its antitumor effect, diosgenin is able to block tumor progression and increase the survival rate of patients with cancer; ultimately improving their quality of life. However, the mechanism underlying its pharmacological action remains unclear. Once tumor cells reach a metastatic phase, it can be fatal. Increased migration and invasiveness are the hallmarks of metastatic tumor cells. Invadopodia formation is key to maintaining the high migration and invasive ability of tumor cells. Invadopodia are a type of membrane structure process rich in filamentous-actin and are common in highly invasive tumor cells. In addition to actin, numerous actin regulators, including cortical actin-binding protein (Cortactin), accumulate in invadopodia. Cortactin is a microfilament actin-binding protein with special repetitive domains that are directly involved in the formation of the cortical microfilament actin cell skeleton. Cortactin is also one of the main substrates of intracellular Src-type tyrosine protein kinases and represents a highly conserved family of intracellular cortical signaling proteins. In recent years, great progress has been made in understanding the role of Cortactin and its molecular mechanism in cell motility. However, the diosgenin-Cortactin-invadopodia mechanism is still under investigation. Therefore, the present review focused on the current research on the regulation of invadopodia by diosgenin via Cortactin. Contents 1. Tumor metastasis 2. Formation and function of invadopodia 3. Antitumor effects and mechanisms of diosgenin 4. Structure and regulation of Cortactin 5. Role of Cortactin in invadopodia formation and function 6. Potential diosgenin-Cortactin-invadopodia mechanism 7. Clinical application of diosgenin 8. Conclusions and prospects

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Cortactin recruits FMNL2 to promote actin polymerization and endosome motility in invadopodia formation

Cited by 31 publications

References 41 publications

Tumor Cellular and Microenvironmental Cues Controlling Invadopodia Formation

Tumor Cellular and Microenvironmental Cues Controlling Invadopodia Formation

A single tyrosine phosphorylation site in cortactin is important for filopodia formation in neuronal growth cones

Inhibition of invadopodia formation by diosgenin in tumor cells (Review)

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