Reduced E-cadherin expression correlates with increased invasiveness in colorectal carcinoma cell lines

Kinsella, Anne R.; Lepts, G. C.; Hill, Charles D.; Jones, Mark

doi:10.1007/bf01753841

Cited by 60 publications

(33 citation statements)

References 16 publications

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“…28 Recent studies have demonstrated that loss of E-cadherin immunoreactivity may correlate with a lack of differentiation and aggressive behavior of breast, head and neck, lung, gastric, esophageal, colorectal, prostatic and urothelial carcinomas. [5][6][7]15,[29][30][31][32][33][34][35] Published studies on urothelial carcinoma show that loss of membranous E-cadherin immunoreactivity is strongly correlated with high grade and advanced stage. 8,12,15,[36][37][38] Whether or not loss of E-cadherin is correlated with disease progression or has any prognostic significance has been debated by several investigators.…”

Section: Discussionmentioning

confidence: 99%

E-cadherin expression in plasmacytoid, signet ring cell and micropapillary variants of urothelial carcinoma: comparison with usual-type high-grade urothelial carcinoma

et al. 2011

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Loss of E-cadherin expression has been linked to the invasive phenotypes of a variety of neoplasms, including lobular breast cancer. The expression of E-cadherin in variants of urothelial carcinoma relative to usual-type urothelial carcinoma, maximum depth of invasion and angiolymphatic invasion has not been well characterized. A total of eight cases of micropapillary urothelial carcinoma, four cases of plasmacytoid urothelial carcinoma, two cases of urothelial carcinoma with signet ring cell differentiation and two cases of urothelial carcinoma with mixed plasmacytoid and signet ring cell differentiation, all obtained from cystectomy/cystoprostatectomy cases, were identified. In all nine cases of usual-type invasive and noninvasive high-grade urothelial carcinoma were also included in the study. Immunohistochemical staining of E-cadherin was performed in all cases. Pathological parameters including depth of invasion and presence of angiolymphatic invasion were documented. Maximum depth of invasion: In micropapillary urothelial carcinoma, extravesical extension was seen in three of eight cases; muscularis propria invasion in four of eight cases; and lamina propria invasion in one of eight cases. In plasmacytoid urothelial carcinoma, extravesical extension was observed in two of four cases, and muscularis propria invasion and lamina propria invasion in one of four cases each. In urothelial carcinoma with signet ring cell differentiation, extravesical extension and muscularis propria invasion was seen in one of two cases each. In urothelial carcinoma with mixed plasmacytoid and signet ring cell differentiation, muscularis propria invasion and lamina propria invasion was observed in one of two cases each. In usual-type high-grade urothelial carcinoma, extravesical extension was seen in six of nine cases and noninvasive in three of nine cases. In angiolymphatic invasion, micropapillary urothelial carcinoma was observed in eight of eight cases; plasmacytoid urothelial carcinoma in two of four cases; urothelial carcinoma with signet ring cell differentiation in one of two cases; and urothelial carcinoma with mixed plasmacytoid and signet ring cell differentiation in one of two cases. Usual-type high-grade urothelial carcinoma was seen in six of nine cases. E-cadherin expression: All eight cases of micropapillary urothelial carcinoma were positive for E-cadherin in the micropapillary component and adjacent usual-type urothelial carcinoma. The four cases of plasmacytoid urothelial carcinoma, two cases of urothelial carcinoma with signet ring cell differentiation and two cases of urothelial carcinoma with mixed plasmacytoid and signet ring cell differentiation were all negative for E-cadherin. All nine additional cases of usual-type high-grade urothelial carcinoma were diffusely positive for E-cadherin. E-cadherin is diffusely positive in usual-type urothelial carcinoma and micropapillary urothelial carcinoma, irrespective of pathological stage and angiolymphatic invasion. Loss of E-cadherin expression may be a marker of...

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Section: Discussionmentioning

confidence: 99%

E-cadherin expression in plasmacytoid, signet ring cell and micropapillary variants of urothelial carcinoma: comparison with usual-type high-grade urothelial carcinoma

et al. 2011

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“…In colon cancer, downregulation of E-cadherin expression is associated with higher histological grade and a worse prognosis (Van Aken et al, 1993). Reduced E-cadherin expression in colon tumor cells allows cells to invade into collagen and Matrigel (Kinsella et al, 1994). Transcriptional regulation is one of the regulatory steps in controlling E-cadherin expression.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of tumor suppressor Pdcd4 promotes invasion and activates both β-catenin/Tcf and AP-1-dependent transcription in colon carcinoma cells

2007

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Programmed cell death 4 (Pdcd4) is a tumor suppressor that inhibits neoplastic transformation and tumor invasion. Tissue microarray analysis showed that Pdcd4 expression is downregulated in colon adenocarcinoma and carcinoma relative to adjacent normal tissues. To address the issue of whether reduced Pdcd4 expression is sufficient to promote tumor progression, we knocked down Pdcd4 expression in colon tumor HT29 cells using pdcd4 short hairpin RNA (shRNA). Pdcd4 knockdown results in a fibroblast-like transition, while the control cells (expressing LacZ shRNA) remain as clumped similar to the parental cells. In addition, expression of pdcd4 shRNA in HT29 cells promotes invasion. In an effort to characterize the molecular mechanism underlying these observations, we discovered that knockdown of Pdcd4 results in reduction of E-cadherin expression, and accumulation of active b-catenin in the nucleus. The active b-catenin binds with T-cell factor 4 (Tcf4) and activates b-catenin/ Tcf-dependent transcription. Furthermore, Pdcd4 knockdown dramatically increases AP-1-dependent transcription. Thus, the mechanism by which reduced Pdcd4 expression promotes invasion appears to involve the activation of b-catenin/Tcf and AP-1-dependent transcription.

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“…Fluctuations in cell-cell adhesion are thought to be key events in the progression from localized malignancy to metastatic disease and several in-vitro studies have confirmed that E-cadherin acts as a tumour suppressor protein (Vleminckx et al, 1991;Kinsella et al, 1994). Reduced E-cadherin expression has been reported in a variety of human tumours and in many cases these changes correlate with advanced disease .…”

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confidence: 99%

Cadherin–catenin expression in primary colorectal cancer: a survival analysis

et al. 1999

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Summary Both cell adhesion and cell signalling events are mediated by components of the cadherin-catenin complex. Loss of expression of the components of this complex have been shown to correlate with invasive behaviour in many tumour types although their exact role in colorectal cancer remains unclear. Immunohistochemical analysis of the expression of components of the cadherin-catenin complex in colorectal cancers from 60 patients was undertaken. Loss of memberanous expression of E-cadherin, α-catenin and β-catenin was demonstrated in 52%, 85% and 40% of tumours respectively. Focal nuclear expression of β-catenin (< 75% of cells per section), usually associated with cytoplasmic expression, was clearly demonstrated in 19 (32%) tumours while widespread nuclear expression (> 75% of tumour cells per section) was seen in 11 (18%) tumours. Loss of membranous α-catenin expression significantly correlated with tumour dedifferentiation (P = 0.009). There was a trend towards an association between advanced tumour stage and loss of membranous expression of α-catenin or β-catenin, although these associations were not statistically significant. Univariate analysis revealed that advanced Dukes' stage, tumour de-differentiation, loss of membranous β-catenin expression, cytoplasmic β-catenin expression and widespread nuclear expression of β-catenin all correlated with short survival following apparently curative resection of the primary tumour. However, only Dukes' stage (P = 0.002), tumour grade (P = 0.02) and widespread nuclear expression of β-catenin (P = 0.002) were independent predictors of short survival. Disturbed growth signalling events in colorectal tumours are thought to result in nuclear accumulation of β-catenin. Consequently, tumours with widespread nuclear expression of β-catenin are likely to have severely abnormal growth characteristics, and which therefore might be predictive of short survival in these patients.

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Reduced E-cadherin expression correlates with increased invasiveness in colorectal carcinoma cell lines

Cited by 60 publications

References 16 publications

E-cadherin expression in plasmacytoid, signet ring cell and micropapillary variants of urothelial carcinoma: comparison with usual-type high-grade urothelial carcinoma

E-cadherin expression in plasmacytoid, signet ring cell and micropapillary variants of urothelial carcinoma: comparison with usual-type high-grade urothelial carcinoma

Downregulation of tumor suppressor Pdcd4 promotes invasion and activates both β-catenin/Tcf and AP-1-dependent transcription in colon carcinoma cells

Cadherin–catenin expression in primary colorectal cancer: a survival analysis

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