Notch increases the shedding of HB-EGF by ADAM12 to potentiate invadopodia formation in hypoxia

Díaz, Begoña; Yuen, Angela; Iizuka, Shinji; Higashiyama, Shigeki; Courtneidge, Sara A.

doi:10.1083/jcb.201209151

Cited by 140 publications

(166 citation statements)

References 96 publications

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“…In cancer cells, epidermal growth factor (EGF) is a well-described inducer of invadopodia formation (Mader et al, 2011;Yamaguchi et al, 2005). TGF-b (Mandal et al, 2008;Pignatelli et al, 2012), heparin binding (HB)-EGF (Díaz et al, 2013;Hayes et al, 2012), VEGF (Lucas et al, 2010) and hepatocyte growth factor/scatter factor (HGF) (Rajadurai et al, 2012) increase invadopodia numbers, whereas stromal cell derived factor 1a (SDF1a) has been shown to increase ECM degradation by breast cancer cells (Smith-Pearson et al, 2010). Many of these growth factor pathways converge on common signaling hubs, especially Src (1) Invadopodia/ podosome initiation.…”

Section: Regulation Of Invadopodia and Podosome Formation By Growth Fmentioning

confidence: 99%

“…MT1-MMP can release growth factors (indicated by the red flash) by multiple mechanisms, including cleavage of the TGFb-binding protein, latencyassociated protein (red, LAP-b1 complex) to release active TGF-b1 (Mu et al, 2002). In addition, MT1-MMP also cleaves HB-EGF, which then releases an EGF-like domain (EGF-L) that could activate EGFR and trigger invadosome initiation (Díaz et al, 2013;Hayes et al, 2012;Koshikawa et al, 2010). (ii) MT1-MMP also cleaves other proteinases such as MMP2 (Sato et al, 1994).…”

Section: Regulation Of Invadopodia and Podosome Formation By Growth Fmentioning

confidence: 99%

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Signaling inputs to invadopodia and podosomes

Hoshino

Branch

Weaver

2013

Journal of Cell Science

153

175

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SummaryRemodeling of extracellular matrix (ECM) is a fundamental cell property that allows cells to alter their microenvironment and move through tissues. Invadopodia and podosomes are subcellular actin-rich structures that are specialized for matrix degradation and are formed by cancer and normal cells, respectively. Although initial studies focused on defining the core machinery of these two structures, recent studies have identified inputs from both growth factor and adhesion signaling as crucial for invasive activity. This Commentary will outline the current knowledge on the upstream signaling inputs to invadopodia and podosomes and their role in governing distinct stages of these invasive structures. We discuss invadopodia and podosomes as adhesion structures and highlight new data showing that invadopodia-associated adhesion rings promote the maturation of already-formed invadopodia. We present a model in which growth factor stimulation leads to phosphoinositide 3-kinase (PI3K) activity and formation of invadopodia, whereas adhesion signaling promotes exocytosis of proteinases at invadopodia.

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Section: Regulation Of Invadopodia and Podosome Formation By Growth Fmentioning

confidence: 99%

Section: Regulation Of Invadopodia and Podosome Formation By Growth Fmentioning

confidence: 99%

Signaling inputs to invadopodia and podosomes

Hoshino

Branch

Weaver

2013

Journal of Cell Science

153

175

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“…A recent studied showed that hypoxia activates the cell contact-dependent Notch signaling pathway to induce invadopodia formation in cancer cells. 62 But can stromal cells influence invadopodia formation in tumor cells? Studies have shown that macrophages induce invadopodia formation in cancer cells through direct cell contact, and facilitate in vitro intravasation via increased RhoA signaling both in breast cancer cell lines and patient-derived tumor cells.…”

Section: Signals From the Tumor Microenvironmentmentioning

confidence: 99%

“…For example, secretion of HB-EGF drives invadopodia formation and matrix degradation in both an autocrine and paracrine manner. 62,72 In head and neck squamous cell carcinoma (HNSCC) cells, inhibition of Abl or Arg tyrosine kinases stimulates HB-EGF shedding. Elevated HB-EGF then leads to hyperactivation of EGFR signaling and Src activity, which results in cortactin phosphorylation and upregulation of invadopodia in an autocrine manner.…”

Section: Growth Factorsmentioning

confidence: 99%

Regulation of invadopodia by the tumor microenvironment

Gould

Courtneidge

2014

Cell Adhesion & Migration

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“…However, there is no evidence yet that ligand-independent EGFR signalling promotes filopodia formation. In contrast, heparin-binding EGF-like growth factor (HB-EGF), an EGFR ligand, regulates invadopodia (43) and invasion (44) via EGFR activation in some cancers. Thus, the HB-EGF/EGFR pathway is likely involved in regulating filopodia formation in SAS cells.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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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.

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Notch increases the shedding of HB-EGF by ADAM12 to potentiate invadopodia formation in hypoxia

Abstract: Hypoxia increases the levels of ADAM12 in a Notch-dependent manner, leading to increased ectodomain shedding of HB-EGF and subsequent promotion of invadopodia formation.

Cited by 140 publications

References 96 publications

Signaling inputs to invadopodia and podosomes

Signaling inputs to invadopodia and podosomes

Regulation of invadopodia by the tumor microenvironment

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

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