Expression of the αvβ6 Integrin Promotes Migration and Invasion in Squamous Carcinoma Cells

Thomas, Gareth J.; Lewis, Mark P.; Whawell, Simon A.; Russell, Alan J.; Sheppard, Dean; Hart, Ian R.; Speight, Paul M.; Marshall, John F.

doi:10.1046/j.0022-202x.2001.01379.x

Cited by 122 publications

(148 citation statements)

References 56 publications

Supporting

Mentioning

139

Contrasting

Unclassified

Order By: Relevance

“…This observation is in accordance with various studies that have reported the role of integrin β 6 in mediating metastasis 15, 34, 35. However, as indicated on the graph (Fig.…”

Section: Discussionsupporting

confidence: 93%

“…In an evolving tumor, the stromal cues bring about changes in the extracellular matrix leading to activation of a family of integrins that mediate attachment of tumor cells to the extracellular matrix (ECM) 13. Components of the ECM, like fibronectin and tenascin and the latency‐associated peptide 1 and 3 have been shown to activate α v β 6 integrin leading to local activation of TGF β 1 signaling at tumor‐stroma interface facilitating tumor migration and invasion 14, 15, 16, 17.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

High expression of integrin β6 in association with the Rho–Rac pathway identifies a poor prognostic subgroup within HER2 amplified breast cancers

et al. 2016

View full text Add to dashboard Cite

Integrin αvβ6 is involved in the transition from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) of the breast. In addition, integrin β6 (ITGB6) is of prognostic value in invasive breast cancers, particularly in HER2+ subtype. However, pathways mediating the activity of integrin αvβ6 in clinical progression of invasive breast cancers need further elucidation. We have examined human breast cancer specimens (N = 460) for the expression of integrin β6 (ITGB6) mRNA by qPCR. In addition, we have examined a subset (N = 147) for the expression of αvβ6 integrin by immunohistochemistry (IHC). The expression levels of members of Rho–Rac pathway including downstream genes (ACTR2,ACTR3) and effector proteinases (MMP9,MMP15) were estimated by qPCR in the HER2+ subset (N = 59). There is a significant increase in the mean expression of ITGB6 in HER2+ tumors compared to HR+HER2‐ and triple negative (TNBC) subtypes (P = 0.00). HER2+ tumors with the highest levels (top quartile) of ITGB6 have significantly elevated levels of all the genes of the Rho–Rac pathway (P‐values from 0.01 to 0.0001). Patients in this group have a significantly shorter disease‐free survival compared to the group with lower ITGB6 levels (HR = 2.9 (0.9–8.9), P = 0.05). The mean level of ITGB6 expression is increased further in lymph node‐positive tumors. The increased regional and distant metastasis observed in HER2+ tumors with high levels of ITGB6 might be mediated by the canonical Rho–Rac pathway through increased expression of MMP9 and MMP15.

show abstract

“…This observation is in accordance with various studies that have reported the role of integrin β 6 in mediating metastasis 15, 34, 35. However, as indicated on the graph (Fig.…”

Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

High expression of integrin β6 in association with the Rho–Rac pathway identifies a poor prognostic subgroup within HER2 amplified breast cancers

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Among these, ␣v␤3 and ␣v␤6 could be the targets because both of them act as the important receptors for fibronectin, and both of them are deeply implicated in the promotion of the cancer cell metastasis (52)(53)(54)(55). One more important molecule that could not be ignored is E-cadherin, which plays critical roles in cell-cell adhesion.…”

Section: Discussionmentioning

confidence: 99%

Expression of N-Acetylglucosaminyltransferase III Suppresses α2,3-Sialylation, and Its Distinctive Functions in Cell Migration Are Attributed to α2,6-Sialylation Levels

Isaji

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

N-Acetylglucosaminyltransferase III (GnT-III), which catalyzes the addition of the bisecting GlcNAc branch on N-glycans, is usually described as a metastasis suppressor. Overexpression of GnT-III inhibited migration in multiple types of tumor cells. However, these results seem controversial to the clinical observations for the increased expression of GnT-III in human hepatomas, glioma, and ovarian cancers. Here, we present evidence that these inconsistencies are mainly attributed to the different expression pattern of cell sialylation. In detail, we show that overexpression of GnT-III significantly inhibits ␣2,3-sialylation but not ␣2,6-sialylation. The migratory ability of cells without or with a low level of ␣2,6-sialylation is consistently suppressed after GnT-III overexpression. In contrast, the effects of GnT-III overexpression are variable in tumor cells that are highly ␣2,6-sialylated. Overexpression of GnT-III promotes the cell migration in glioma cells U-251 and hepatoma cells HepG2, although it has little influence in human breast cancer cell MDA-MB-231 and gastric cancer cell MKN-45. Interestingly, up-regulation of ␣2,6-sialylation by overexpressing ␤-galactoside ␣2,6-sialyltranferase 1 in the ␣2,6-hyposialylated HeLa-S3 cells abolishes the anti-migratory effects of GnT-III. Conversely, depletion of ␣2,6-sialylation by knock-out of ␤-galactoside ␣2,6-sialyltranferase 1 in ␣2,6-hypersialylated HepG2 cells endows GnT-III with the anti-migratory ability. Taken together, our data clearly demonstrate that high expression of ␣2,6-sialylation on the cell surface could affect the anti-migratory role of GnT-III, which provides an insight into the mechanistic roles of GnT-III in tumor metastasis.Alterations in N-linked glycosylation have been observed in various malignant diseases such as cancer. Certain glycan structures resulting from the dysregulated glycosyltransferases and glycosidases are well known tumor markers and closely associated with the malignant progression (1). As examples, the ␣1,6-fucosylated ␣-fetoprotein catalyzed by ␣1,6-fucosyltransferase has been developed as a biomarker for primary hepatoma by Abelev (2). An increase in ␤1,6-GlcNAc branching of N-glycans as a consequence of enhanced expression of N-acetylglucosaminyltransferase V (GnT-V) 2 is convincingly correlated with the increased frequency of tumor metastasis (3-6). N-Acetylglucosaminyltransferase III (GnT-III) is one more important glycosyltransferase that has been receiving much attention for its involvement in the biology of tumor (7,8). It catalyzes the transfer of N-acetylglucosamine (GlcNAc) in a ␤1,4 linkage to mannose on N-glycans forming a bisecting GlcNAc structure. This step plays critical roles in determining the structure of N-glycans because introduction of the bisecting GlcNAc residue could preclude further processing and elongation of N-glycans, such as the formation of ␤1,6-GlcNAc branching structures (9). Considering also that overexpression of GnT-III inhibited the metastasis of multiple types of carcinomas (10, 1...

show abstract

“…A panel of three oral SCC cell lines were used. We generated the invasive VB6 cell line previously by transfection and retroviral infection of integrin subunits to express high levels of the integrin avb6 (Thomas et al, 2001b). CA1 and 5PT were kind gifts from Professor IC Mackenzie (Cardiff dental School, UK).…”

Section: Cell Culturementioning

confidence: 99%

Tumour-derived TGF-β1 modulates myofibroblast differentiation and promotes HGF/SF-dependent invasion of squamous carcinoma cells

et al. 2004

View full text Add to dashboard Cite

The development of an altered stromal microenvironment is a common feature of many tumours including squamous cell carcinoma (SCC), and there is increasing evidence that these changes in the stroma, which include increased expression of proteases and cytokines, may actually promote tumour progression. A common finding is that stromal fibroblasts become 'activated' myofibroblasts, expressing smooth muscle actin and secreting cytokines, proteases and matrix proteins. We show that myofibroblasts are commonly found in the stroma of oral SCC and are often concentrated at the invasive margin of the tumour. Using oral SCC cells and primary oral fibroblasts, we demonstrate that tumour cells directly induce a myofibroblastic phenotype, and that this transdifferentiation is dependent on SCC-derived TGF-b1. In turn, myofibroblasts secrete significantly higher levels of hepatocyte growth factor/scatter factor compared with fibroblast controls, and this cytokine promotes SCC invasion through Matrigel, a mixture of basement membrane proteins. This is the first time that this double paracrine mechanism has been demonstrated between squamous carcinoma cells and fibroblasts, and emphasises that cancer invasion can be promoted indirectly by the release of tumour-induced host factors from stroma.

show abstract

Expression of the αvβ6 Integrin Promotes Migration and Invasion in Squamous Carcinoma Cells

Cited by 122 publications

References 56 publications

High expression of integrin β6 in association with the Rho–Rac pathway identifies a poor prognostic subgroup within HER2 amplified breast cancers

High expression of integrin β6 in association with the Rho–Rac pathway identifies a poor prognostic subgroup within HER2 amplified breast cancers

Expression of N-Acetylglucosaminyltransferase III Suppresses α2,3-Sialylation, and Its Distinctive Functions in Cell Migration Are Attributed to α2,6-Sialylation Levels

Tumour-derived TGF-β1 modulates myofibroblast differentiation and promotes HGF/SF-dependent invasion of squamous carcinoma cells

Contact Info

Product

Resources

About