Reduced expression of alpha catenin is associated with poor prognosis in colorectal carcinoma

Ropponen, Kirsi; Eskelinen, Matti; Lipponen, P; Alhava, Esko; Kosma, Veli‐Matti

doi:10.1136/jcp.52.1.10

Cited by 31 publications

(21 citation statements)

References 21 publications

(24 reference statements)

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“…Our data show that loss of CAR impairs the expression of a-catenin, a protein that has been extensively studied for its inhibition of cancer cell growth and motility (Scott and Yap, 2006). Moreover, loss of a-catenin is frequently described in carcinomas, for example, colon cancer, significantly correlating with depth of invasion, presence of metastasis, and an adverse clinical outcome (Ropponen et al, 1999). In line with these reports, we noted an increased proliferation, migration, and invasion after loss of CAR and a-catenin.…”

Section: Discussionmentioning

confidence: 92%

Loss of Coxsackie and adenovirus receptor downregulates α-catenin expression

et al. 2009

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BACKGROUND: The Coxsackie and adenovirus receptor (CAR) has been shown to inhibit cancer cell proliferation, migration, and invasion. The underlying mechanisms, however, are poorly understood. METHODS: The differential gene expression in the human colon cancer cell line DLD1 on RNAi-mediated functional CAR knockdown was analysed using oligo-array technology. Expression of a-catenin was determined by quantitative RT-PCR and western blotting. Proliferation, migration, and invasion after CAR knockdown were assessed by in vitro assays, and cell morphology in a threedimensional context was evaluated using matrigel. RESULTS: Oligo-array technology identified a-catenin as the strongest downregulated gene after CAR knockdown. Western blotting and quantitative RT-PCR confirmed a reduced a-catenin expression after CAR knockdown in DLD1 cells and in the rat intestinal cell line IEC-6. Functionally, both cell lines showed a marked increase in proliferation, migration, and invasion on CAR knockdown. In matrigel, both cell lines formed amorphous cell clusters in contrast to well-organised three-dimensional structures of CAR-expressing vector controls. Ectopic 're'-expression of a-catenin in DLD1 and IEC-6 CAR knockdown cells reversed these functional and morphological effects. CONCLUSION: These data suggest that an interaction of CAR and a-catenin mediates the impact of CAR on cell proliferation, migration, invasion, and morphology.

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Section: Discussionmentioning

confidence: 92%

Loss of Coxsackie and adenovirus receptor downregulates α-catenin expression

et al. 2009

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“…The positivity of endothelia and myofiblasts served as an inner positive control. The intensity of the staining was scored as negative (0), weak (1), moderate (2), or strong (3) (Ropponen et al, 1999). All staining scores are averages of duplicate experiments, and all samples were independently scored by two of us (TC and HE) who were blinded to the patient status.…”

Section: Immunohistochemistrymentioning

confidence: 99%

miR-145 and miR-133a function as tumour suppressors and directly regulate FSCN1 expression in bladder cancer

et al. 2010

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BACKGROUND: We have recently identified down-regulated microRNAs including miR-145 and miR-133a in bladder cancer (BC). The aim of this study is to determine the genes targeted by miR-145, which is the most down-regulated microRNA in BC. METHODS: We focused on fascin homologue 1 (FSCN1) from the gene expression profile in miR-145 transfectant. The luciferase assay was used to confirm the actual binding sites of FSCN1 mRNA. Cell viability was evaluated by cell growth, wound-healing, and matrigel invasion assays. BC specimens were subjected to immunohistochemistry of FSCN1 and in situ hybridisation of miR-145. RESULTS: The miR-133a as well as miR-145 had the target sequence of FSCN1 mRNA by the database search, and both microRNAs repressed the mRNA and protein expression of FSCN1. The luciferase assay revealed that miR-145 and miR-133a were directly bound to FSCN1 mRNA. Cell viability was significantly inhibited in miR-145, miR-133a, and si-FSCN1 transfectants. In situ hybridisation revealed that miR-145 expression was markedly repressed in the tumour lesion in which FSCN1 was strongly stained. The immunohistochemical score of FSCN1 in invasive BC (n ¼ 46) was significantly higher than in non-invasive BC (n ¼ 20) (P ¼ 0.0055). CONCLUSION: Tumour suppressive miR-145 and miR-133a directly control oncogenic FSCN1 in BC.

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“…A disruption of these interactions may lead to a destabilization of adherens junctions and a cytoplasmic rather than junctional localization of E-cadherin. For example, a reduced expression of ·-catenin (which mediates connection of the E-cadherin/catenin complex to actin cytoskeleton), has been frequently reported in colorectal cancers and may result in the cytoplasmic relocation of E-cadherin (56). How a loss of palladin expression leads to the disruption of adherens junctions in HCT116 cells is unclear.…”

Section: Discussionmentioning

confidence: 99%

Palladin, an actin-associated protein, is required for adherens junction formation and intercellular adhesion in HCT116 colorectal cancer cells

Tay

Tan²,

Lan³

et al. 2010

Int J Oncol

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Abstract. Palladin is a scaffold protein involved in the formation of actin-associated protein complexes. Gene expression array analysis on the poorly metastatic HCT116 colon cancer cell line and a metastatic derivative cell line (E1) with EMT (epithelial-mesenchymal transition) features showed a down-regulation of palladin gene expression in the latter. Knockdown of palladin expression in the HCT116 cells suppressed junctional localization of E-cadherin, reduced intercellular adhesion and collective cell migration, showing that palladin plays an important role in maintaining the integrity of adherens junctions. The acquisition of the EMT features by the E1 cell line was dependent on the Erk pathway. Inhibition of this pathway by U0126 treatment in E1 cells resulted in the re-expression of palladin, relocalization of E-cadherin to the adherens junctions and a reversal of EMT features. The re-establishment of intercellular adhesion was dependent on palladin expression. The down-regulation of palladin was also observed in poorly-differentiated tumor tubules and dissociated tumor cells that have undergone de-differentiation in human primary colon tumors. Our data show that palladin is an integral component of adherens junctions and plays a role in the localization of E-cadherin to the junctions. The loss of palladin may be an integral part of EMT, an early step in the metastatic spread of colon carcinoma.

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Reduced expression of alpha catenin is associated with poor prognosis in colorectal carcinoma

Cited by 31 publications

References 21 publications

Loss of Coxsackie and adenovirus receptor downregulates α-catenin expression

Loss of Coxsackie and adenovirus receptor downregulates α-catenin expression

miR-145 and miR-133a function as tumour suppressors and directly regulate FSCN1 expression in bladder cancer

Palladin, an actin-associated protein, is required for adherens junction formation and intercellular adhesion in HCT116 colorectal cancer cells

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