Lamellipodin and the Scar/WAVE complex cooperate to promote cell migration in vivo

Law, Ah-Lai; Vehlow, Anne; Kotini, Maria P.; Dodgson, Lauren; Soong, Daniel; Théveneau, Eric; Bodo, Cristian; Taylor, Eleanor; Navarro, Christel; Perera, Upamali; Michael, Magdalene; Dunn, Graham; Bennett, Daimark; Mayor, Roberto; Krause, Matthias

doi:10.1083/jcb.201304051

Cited by 118 publications

(193 citation statements)

References 55 publications

(113 reference statements)

Supporting

Mentioning

172

Contrasting

Unclassified

Order By: Relevance

“…These results are consistent with previous reports that HGF/c-Met signalling promoted cell migration through lamellipodia and filopodia formation in lung endothelial cells (28) and in some normal cells (30). Thus, it is possible that lamellipodia and filopodia formation is regulated by c-Met signalling, thereby promoting the migration of OSCC cells.…”

Section: Discussionsupporting

confidence: 82%

“…In this context, we showed that c-Met signalling was involved in the regulation of lamellipodin protein levels. Promotion of cell migration potency via the c-Met pathway is possibly regulated by increasing the level of lamellipodin, because upregulation of lamellipodin protein markedly promoted cell migration (30).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, lamellipodin, a protein necessary for the formation of lamellipodia, has been reported to be important in cell migration via interactions with the Ena/VASP or Scar/WAVE complex (29,30). Although Wnt signalling promotes formation of pseudopodia by the stimulating Cdc42 and RhoA in OSCC (31), other protein levels and signalling pathways necessary for the formation of pseudopodia in OSCC have yet to be determined.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Migration of oral squamous cell carcinoma cells are induced by HGF/c-Met signalling via lamellipodia and filopodia formation

et al. 2017

View full text Add to dashboard Cite

Abstract. The activation of receptor tyrosine kinases (RTKs) results in cellular effects including cell proliferation, survival, migration and invasion; RTKs also play an important role in tumourigenesis. It has been reported that EGFR signalling controls the migration of oral squamous cell carcinoma (OSCC) SAS and HSC3 cells but not of HSC4 cells, although the proliferation of HSC4 cells is regulated by EGF/EGFR. In the present study, we investigated the roles of EGFR and the c-Met signalling pathway in cell migration via filopodia and lamellipodia formation, which may be prerequisites for migration. To explore the role of c-Met in cell migration, we inhibited c-Met RTK activity using the c-Met inhibitor SU11274 and activated c-Met using hepatocyte growth factor (HGF) in three OSCC cell lines HSC4, SAS and Ca9-22 and investigated migration potency using a wound healing assay. We showed that inhibition of c-Met significantly suppressed, and activation of c-Met significantly promoted, the migration of OSCC cells. Additionally, the migration of SAS and Ca9-22 cells was inhibited by the EGFR inhibitors AG1478 and cetuximab and promoted by EGF treatment. Moreover, migration potency was correlated with lamellipodia formation. Furthermore, western blot analyses demonstrated that SU11274 decreased and HGF increased lamellipodin protein levels as well as phosphorylated c-Met levels. Collectively, we demonstrated that c-Met signalling induced lamellipodia formation by upregulating lamellipodin, thereby promoting the migration of OSCC cells.

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Migration of oral squamous cell carcinoma cells are induced by HGF/c-Met signalling via lamellipodia and filopodia formation

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Lpd is an actin-remodeling protein reported to bind PI(3,4)P2 (30) and to regulate random motility in nonhematopoietic cells (34). To determine whether Lpd may be a mediator of PI(3,4)P2-dependent chemotaxis in malignant B cells, we first examined expression of Lpd in human B cells and found that Lpd is expressed in a variety of malignant B cell lines and primary CLL B cells (Fig.…”

Section: Lpd Is Expressed In Malignant B Cells and Colocalizes With Pmentioning

confidence: 99%

“…Lpd was shown to mediate random motility in breast cancer cells (29,34) as well as extension of neuronal processes (35). It remains unknown whether Lpd is involved in directional migration in response to specific chemotactic stimuli, and whether the function of Lpd in promoting cell migration depends on its PI(3,4)P2-binding PH domain.…”

mentioning

confidence: 99%

Phosphatidylinositol-3,4-Bisphosphate and Its Binding Protein Lamellipodin Regulate Chemotaxis of Malignant B Lymphocytes

Hou

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

Cell migration is controlled by PI3Ks, which generate lipid messengers phosphatidylinositol-3,4,5-trisphosphate and phosphatidylinositol-3,4-bisphosphate [PI(3,4)P2] and consequently recruit pleckstrin homology (PH) domain–containing signaling proteins. PI3K inhibition impairs migration of normal and transformed B cells, an effect thought to partly underlie the therapeutic efficacy of PI3K inhibitors in treatment of B cell malignancies such as chronic lymphocytic leukemia. Although a number of studies have implicated phosphatidylinositol-3,4,5-trisphosphate in cell migration, it remains unknown whether PI(3,4)P2 plays a distinct role. Using the PI(3,4)P2-specific phosphatase inositol polyphosphate 4-phosphatase, we investigate the impact of depleting PI(3,4)P2 on migration behavior of malignant B cells. We find that cells expressing wild-type, but not phosphatase dead, inositol polyphosphate 4-phosphatase show impaired SDF-induced PI(3,4)P2 responses and reduced migration in Transwell chamber assays. Moreover, PI(3,4)P2 depletion in primary chronic lymphocytic leukemia cells significantly impaired their migration capacity. PI(3,4)P2 depletion reduced both overall motility and migration directionality in the presence of a stable chemokine gradient. Within chemotaxing B cells, the PI(3,4)P2-binding cytoskeletal regulator lamellipodin (Lpd) was found to colocalize with PI(3,4)P2 on the plasma membrane via its PH domain. Overexpression and knockdown studies indicated that Lpd levels significantly impact migration capacity. Moreover, the ability of Lpd to promote directional migration of B cells in an SDF-1 gradient was dependent on its PI(3,4)P2-binding PH domain. These results demonstrate that PI(3,4)P2 plays a significant role in cell migration via binding to specific cytoskeletal regulators such as Lpd, and they suggest that impairment of PI(3,4)P2-dependent processes may contribute to the therapeutic efficacy of PI3K inhibitors in B cell malignancies.

show abstract

dAsap regulates cellular protrusions via an Arf6‐dependent actin regulatory pathway in S2R+ cells

Kushwaha,

Mallik,

Bisht

et al. 2024

FEBS Letters

View full text Add to dashboard Cite

Membrane protrusions are fundamental to cellular functions like migration, adhesion, and communication and depend upon dynamic reorganization of the cytoskeleton. GAP‐dependent GTP hydrolysis of Arf proteins regulates actin‐dependent membrane remodeling. Here, we show that dAsap regulates membrane protrusions in S2R+ cells by a mechanism that critically relies on its ArfGAP domain and relocalization of actin regulators, SCAR, and Ena. While our data reinforce the preference of dAsap for Arf1 GTP hydrolysis in vitro, we demonstrate that induction of membrane protrusions in S2R+ cells depends on Arf6 inactivation. This study furthers our understanding of how dAsap‐dependent GTP hydrolysis maintains a balance between active and inactive states of Arf6 to regulate cell shape.

show abstract

Lamellipodin and the Scar/WAVE complex cooperate to promote cell migration in vivo

Abstract: Lpd is an essential, evolutionary conserved regulator of the Scar/WAVE complex during cell migration in vivo.

Cited by 118 publications

References 55 publications

Migration of oral squamous cell carcinoma cells are induced by HGF/c-Met signalling via lamellipodia and filopodia formation

Migration of oral squamous cell carcinoma cells are induced by HGF/c-Met signalling via lamellipodia and filopodia formation

Phosphatidylinositol-3,4-Bisphosphate and Its Binding Protein Lamellipodin Regulate Chemotaxis of Malignant B Lymphocytes

dAsap regulates cellular protrusions via an Arf6‐dependent actin regulatory pathway in S2R+ cells

Contact Info

Product

Resources

About