Transforming Growth Factor-β1 Promotes Matrix Metalloproteinase-9–Mediated Oral Cancer Invasion through Snail Expression

Sun, Limin; Diamond, Michelle E.; Ottaviano, Adam J.; Joseph, Mathew J.; Ananthanarayan, Vijayalakshmi; Munshi, Hidayatullah G.

doi:10.1158/1541-7786.mcr-07-0208

Cited by 117 publications

(137 citation statements)

References 53 publications

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“…1 Recently, the EMT has been found to contribute to the progression and confer cancer cells with stem cell-like properties, in which the cells have a propensity for invasion, metastatic dissemination, resistance to certain therapy, persistence in tumours, and recurrence. 19,28 Understanding the molecular and cellular changes may generate novel targets that can overcome the aforementioned issues and reduce mortality.…”

Section: Discussionmentioning

confidence: 99%

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Snail overexpression induces an epithelial to mesenchymal transition and cancer stem cell-like properties in SCC9 cells

Zhu

Yang

et al. 2012

Laboratory Investigation

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Local invasiveness and distant metastasis are critical factors that contribute to oral squamous cell carcinoma-related deaths. Increasing evidence has shown that the epithelial to mesenchymal transition (EMT) is involved in cancer progression and is associated with the 'stemness' of cancer cells. Snail is a transcriptional factor that can induce EMT and preserve stem-cell function, which may induce resistance to radio-and chemotherapies in the cells. In the present study, SCC9 cells were transfected with an empty vector or a vector encoding human Snail (SCC9-S). Overexpression of Snail induced SCC9 cells to undergo EMT, in which the cells presented a fibroblast-like appearance, downregulated the epithelial markers E-cadherin and b-catenin, upregulated the mesenchymal marker vimentin, and associated with highly invasive and metastatic properties. Furthermore, the induction of EMT promoted cancer stem cell (CSC)-like characteristics in the SCC9-S cells, such as low proliferation, self-renewal, and CSC-like markers expression. These results indicate that overexpression of Snail induces EMT and promotes CSC-like traits in the SCC9 cells. Further understanding the role of Snail in cancer progression may reveal new targets for the prevention or therapy of oral cancers. Oral squamous cell carcinoma (OSCC) is the most frequent type of cancer in the oral cavity and is associated with high morbidity and poor prognosis. 1,2 Despite progress in surgery, chemotherapy, and radiotherapy, the 5-year survival rate has remained at 50-55% over the past several decades. 3 Local or regional recurrences and distant metastases have a critical role in this process, and the mechanism underlying their occurrence remains poorly understood. 2,4 During metastatic progression, tumour cells lose cell-cell adhesion, detach from the primary site, invade the basement membrane, survive and circulate in the blood vessels, leave the bloodstream, and finally colonise in a new host environment to form micrometastases. 2,5-7 A growing body of research strongly suggests that the epithelial to mesenchymal transition (EMT), which occurs normally during embryonic development, tissue remodelling, and wound healing, is a critical early event in tumour invasion and metastasis. [8][9][10] It is characterised by downregulation of epithelial markers, such as E-cadherin, and upregulation of mesenchymal markers, such as vimentin. During the process of EMT, epithelial cells acquire mesenchymal cell properties and show reduced intercellular adhesion and increased invasion. 11 The transcriptional repressor Snail, which is a zinc finger protein, first described in Drosophila melanogaster, can bind to the E-boxes in the human E-cadherin promoter and suppress its transcription. 12,13 Snail has previously been implicated in triggering EMT during embryonic development, fibrosis, and tumour progression. 14 This process also occurs in the progression of carcinomas (including oral carcinoma cells), following the downregulation of E-cadherin expression or co-expression of NB...

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Section: Discussionmentioning

confidence: 99%

“…1,2 Despite progress in surgery, chemotherapy, and radiotherapy, the 5-year survival rate has remained at 50-55% over the past several decades. 3 Local or regional recurrences and distant metastases have a critical role in this process, and the mechanism underlying their occurrence remains poorly understood.…”

mentioning

confidence: 99%

Snail overexpression induces an epithelial to mesenchymal transition and cancer stem cell-like properties in SCC9 cells

Zhu

Yang

et al. 2012

Laboratory Investigation

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“…SCC25 cells were routinely maintained in DMEM and Ham's F-12 medium (1:1) containing 10% fetal calf serum and supplemented with 100 units/ml penicillin and 100 g/ml streptomycin (4,30). OKF6 cells were maintained in keratinocyte-SFM supplemented with 100 units/ml penicillin, 100 g/ml streptomycin, 25 g/ml bovine pituitary extract (supplied with the medium), 0.2 ng/ml epidermal growth factor, and 0.31 mM CaCl 2 (31,32).…”

Section: Methodsmentioning

confidence: 99%

Rho-ROCK-Myosin Signaling Meditates Membrane Type 1 Matrix Metalloproteinase-induced Cellular Aggregation of Keratinocytes

Dangi-Garimella

Redig

Shields

et al. 2010

Journal of Biological Chemistry

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Matrix metalloproteinases (MMPs) 2 are a large family of highly conserved metalloendopeptidases with proteolytic activity directed against a variety of extracellular matrix (ECM) substrates (1-3). MMPs have been implicated in basement membrane proteolysis, activation of growth factors, and cleavage of cell-adhesion molecules. Extending mechanistic investigation to cancer biology, numerous studies have shown that MMP overexpression enhances the invasive activity of tumor cell lines (4 -6). Analysis of human disease further supports the pro-tumorigenic role of MMPs, as increased expression of these proteases in tumor samples is clinically associated with invasion, metastasis, poor prognosis, and shorter survival times (7,8). In the specific case of squamous cell carcinoma (SCC), increased expression of membrane type 1-MMP (MT1-MMP, MMP14) is associated with ECM breakdown, tissue invasion, and lymph node metastasis (8).However, several animal studies have now clearly demonstrated that multiple members of the MMP family provide a paradoxically protective effect during the relentless molecular destruction that characterizes malignant progression. MMPs may have been initially identified as potent pro-tumorigenic proteases, but their simultaneous ability to function in an opposing, anti-tumorigenic role is now equally well established (9, 10). Such data underscore both the complexity of MMP activity in cellular signaling events as well as the importance of stringently evaluating the context in which these proteases take on either an anti-tumorigenic or pro-tumorigenic role. Intriguingly, several recent studies using SCC models have begun to suggest a putative mechanism through which MMPs may be induced to function primarily as anti-tumorigenic proteases. When exposed to carcinogens, MMP3-null mice developed squamous cell skin cancers that not only grew faster but were also strikingly less differentiated than those of control animals (11). Significantly, orthotopic injection of MMP3-expressing tumor cells resulted in pronounced tumor cell differentiation (12). However, although such findings indicate that MMPs may inhibit SCC progression by promoting tumor cell differentiation, the precise mechanism through which these proteinases regulate this process has not yet been elucidated.In normal tissue keratinocyte differentiation is a complex process mediated by cell-ECM and cell-cell interactions that subsequently activate downstream signaling pathways (13-15). Specifically, among structural proteins, integrins mediate primarily cell-ECM interactions, whereas cadherins are responsible for cell-cell interactions (13). In vitro activation of integrins or inhibition of cadherins after ligation or dominant negative expression, respectively, results in negative regulation of human keratinocyte differentiation (16 -18). Furthermore, beyond structural proteins, Rho GTPases are also known to be an important component of keratinocyte differentiation pathways. Rho signaling has been shown to mediate cell-cell and cell-matrix adhesion...

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“…Several molecular pathways, once activated, regulate MMP-9 expression: MMP-9 is controlled by the Raf/MEK/ERK cascade and the transcription factors SLUG and NF-jB induce MMP-9 expression (Beliveau et al, 2010;Sun et al, 2008;Moon et al, 2007). Furthermore, the transcriptional stability is maintained through the p38 MAPK/MAPK2 signaling and, interestingly tissue transglutaminase 2 is reported to promote MMP-9 expression (Cai et al, 2011;Kumar et al, 2010;Li et al, 2011).…”

Section: Biological Aspectsmentioning

confidence: 99%

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Sbardella

Fasciglione

Gioia

et al. 2012

Molecular Aspects of Medicine

209

212

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a b s t r a c tHuman matrix metalloproteinases (MMPs) belong to the M10 family of the MA clan of endopeptidases. They are ubiquitarian enzymes, structurally characterized by an active site where a Zn 2+ atom, coordinated by three histidines, plays the catalytic role, assisted by a glutamic acid as a general base. Various MMPs display different domain composition, which is very important for macromolecular substrates recognition. Substrate specificity is very different among MMPs, being often associated to their cellular compartmentalization and/or cellular type where they are expressed. An extensive review of the different MMPs structural and functional features is integrated with their pathological role in several types of diseases, spanning from cancer to cardiovascular diseases and to neurodegeneration. It emerges a very complex and crucial role played by these enzymes in many physiological and pathological processes.

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Transforming Growth Factor-β1 Promotes Matrix Metalloproteinase-9–Mediated Oral Cancer Invasion through Snail Expression

Cited by 117 publications

References 53 publications

Snail overexpression induces an epithelial to mesenchymal transition and cancer stem cell-like properties in SCC9 cells

Snail overexpression induces an epithelial to mesenchymal transition and cancer stem cell-like properties in SCC9 cells

Rho-ROCK-Myosin Signaling Meditates Membrane Type 1 Matrix Metalloproteinase-induced Cellular Aggregation of Keratinocytes

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

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