MT1-MMP Inactivates ADAM9 to Regulate FGFR2 Signaling and Calvarial Osteogenesis

Chan, Kui Ming; Wong, Hoi Leong Xavier; Jin, Guoxiang; Liu, Baohua; Cao, Renhai; Cao, Yihai; Lehti, Kaisa; Tryggvason, Karl; Zhou, Zhongjun

doi:10.1016/j.devcel.2012.04.014

Cited by 71 publications

(86 citation statements)

References 50 publications

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“…MMP-14 degrades extracellular matrix components (i.e. fibrillar collagen and gelatin), activates enzymes such as MMP-2 and MMP-13, sheds cell surface proteins (Chan et al, 2012;Egeblad and Werb, 2002;Itoh and Seiki, 2006;Koshikawa et al, 2011;Koshikawa et al, 2010), and was recently shown to prevent collagen-induced apoptosis (Maquoi et al, 2012). The activity of MMP-14 is regulated by multiple mechanisms, including activation by cell surface proteins such as tetraspanin CD151 and aVb3 integrins (Deryugina et al, 2004;Gonzalo et al, 2010;Hadler-Olsen et al, 2011;Itoh and Seiki, 2004;Yañez-Mó et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

ADAM12 redistributes and activates MMP-14, resulting in gelatin degradation, reduced apoptosis, and increased tumor growth

Albrechtsen

Kveiborg

Stautz

et al. 2013

Journal of Cell Science

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SummaryMatrix metalloproteinases (MMPs), in particular MMP-2, MMP-9 and MMP-14, play a key role in various aspects of cancer pathology. Likewise, ADAMs (a disintegrin and metalloproteinases), including ADAM12, are upregulated in malignant tumors and contribute to the pathology of cancers. Here, we show that there is a positive correlation between MMP-14 and ADAM12 expression in human breast cancer. We demonstrated that in 293-VnR and human breast cancer cells expressing ADAM12 at the cell surface, endogenous MMP-14 was recruited to the cell surface, resulting in its activation. Subsequent to this activation, gelatin degradation was stimulated and tumor cell apoptosis was decreased, with reduced expression of the pro-apoptotic proteins BCL2L11 and BIK. The effect on gelatin degradation was abrogated by inhibition of the MMP-14 activity and appeared to be dependent on cell surface aVb3 integrin localization, but neither the catalytic activity of ADAM12 nor the cytoplasmic tail of ADAM12 were required. The significance of ADAM12-induced activation of MMP-14 was underscored by a reduction in MMP-14-mediated gelatin degradation and abolition of apoptosis-protective effects by specific monoclonal antibodies against ADAM12. Furthermore, orthotopic implantation of ADAM12-expressing MCF7 cells in nude mice produced tumors with increased levels of activated MMP-14 and confirmed that ADAM12 protects tumor cells against apoptosis, leading to increased tumor progression. In conclusion, our data suggest that a ternary protein complex composed of ADAM12, aVb3 integrin and MMP-14 at the tumor cell surface regulates the function of MMP-14. This interaction might point to a novel concept for the development of MMP-14-targeting drugs in treating cancer.

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Section: Introductionmentioning

confidence: 99%

ADAM12 redistributes and activates MMP-14, resulting in gelatin degradation, reduced apoptosis, and increased tumor growth

Albrechtsen

Kveiborg

Stautz

et al. 2013

Journal of Cell Science

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“…Thus, cell invasion into dense matrices, such as basement membranes, requires ECM proteolysis and remodeling to clear space and create tracks along which cells can migrate more efficiently (Hotary et al, 2006;Sabeh et al, 2004;Sabeh et al, 2009). Cell-associated proteolytic activity is also likely to be important for cleavage of non-ECM targets, including latent growth factors and integrins (Black et al, 1997;Chan et al, 2012;Izumi et al, 1998;Kajita et al, 2001;Kessenbrock et al, 2010;Koshikawa et al, 2010;Lyons et al, 1990;Moss et al, 1997;Mu et al, 2002;Turk et al, 2001;Yu and Stamenkovic, 2000).…”

Section: Introductionmentioning

confidence: 99%

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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“…1). 9 These data suggested that MT1-MMP is tightly connected with FGF signaling in calvarial development.…”

Section: Mt1-mmp As a Positive Modulator Of Fgf Signalingmentioning

confidence: 89%

“…1). 9 It is interesting that ADAM9-mediated cleavage of FGFR2 results in the formation of C-terminally truncated fragments with unclear functions. It is likely that the accumulation of truncated FGFR2 fragments inhibits FGF signaling in a dominant-negative manner, but further investigation will be required to confirm that.…”

Section: Mt1-mmp and Fgf Signaling In Intramembranous Ossificationmentioning

confidence: 99%

When MT1-MMP meets ADAMs

et al. 2012

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MT1-MMP Inactivates ADAM9 to Regulate FGFR2 Signaling and Calvarial Osteogenesis

Cited by 71 publications

References 50 publications

ADAM12 redistributes and activates MMP-14, resulting in gelatin degradation, reduced apoptosis, and increased tumor growth

ADAM12 redistributes and activates MMP-14, resulting in gelatin degradation, reduced apoptosis, and increased tumor growth

Signaling inputs to invadopodia and podosomes

When MT1-MMP meets ADAMs

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