αE‐catenin is a candidate tumor suppressor for the development of E‐cadherin‐expressing lobular‐type breast cancer

Groot, Jolien S. de; Rätze, Max A K; Amersfoort, Miranda van; Eisemann, Tanja; Vlug, Eva J.; Niklaas, Mijanou T.; Chin, Suet Feung; Caldas, Carlos; Diest, Paul J. van; Jonkers, Jos; Rooij, Johan de; Derksen, Patrick W.B.

doi:10.1002/path.5099

Cited by 37 publications

(33 citation statements)

References 41 publications

(65 reference statements)

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“…Intriguingly, over 50% of early diffuse gastric cancers in a Korean study had reduced or absent catenin alpha-1 expression [11]. Expression loss was likely due to purely somatic gene inactivation (tumoral mutations, epigenetic changes), as shown in invasive lobular carcinoma of the breast, considering the rarity of CTNNA1 germline mutations [12]. The high proportion of DGC losing catenin alpha-1 expression in the Korean paper contrasts with our observations, and these discrepancies warrant further exploration in future studies.…”

Section: Discussionmentioning

confidence: 99%

Clinical implications of CTNNA1 germline mutations in asymptomatic carriers

et al. 2018

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In 2017, we implemented CTNNA1 germline analysis in probands suspected of having hereditary diffuse gastric cancer. Here, we report the results from a retrospective series of 41 cases, including the identification of a new family with a CTNNA1 mutation and the first prophylactic total gastrectomy in an asymptomatic carrier after a normal upper endoscopy. Diffuse gastric cancer foci with loss of catenin alpha-1 expression were seen in the resected tissue, suggesting that CTNNA1 and CDH1 germline mutations behave in a similar manner. Life-changing prophylactic total gastrectomy should therefore also be considered in CTNNA1 mutation carriers.

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Section: Discussionmentioning

confidence: 99%

Clinical implications of CTNNA1 germline mutations in asymptomatic carriers

et al. 2018

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“… 18 , 19 The down-regulation or absence of CTNNA1 expression may lead to the dysfunction of E-cadherin/catenin complex, which leads to the loss of contact inhibition between cells and the enhancement of tumor cell proliferation and invasion. 20 CTNNA1 gene is located on chromosome 5q31, and the protein encoded by CTNNA1 gene is generally expressed in normal tissues, but down-regulated in some tumor tissues, and is closely related to tumor progression and prognosis, such as gastric cancer, 21 breast cancer 22 and colon cancer. 23 However, the function and mechanism of CTNNA1 in BLCA are still unclear.…”

Section: Introductionmentioning

confidence: 99%

<p>α-E-Catenin (CTNNA1) Inhibits Cell Proliferation, Invasion and EMT of Bladder Cancer</p>

Chi¹,

Xu²,

Song³

et al. 2020

CMAR

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Aim Bladder cancer (BLCA) is an urogenital system tumor with a high morbidity. We aimed to explore the function and potential mechanism of α-E-catenin (CTNNA1) in BLCA. Methods The CTNNA1 expression in BLCA tissues was detected using qRT-PCR and immunohistochemistry. QRT-PCR and Western blot were performed to measure the CTNNA1 expression in BLCA cell lines. CTNNA1 expression was up-regulated in T24 and UMUC-2 cells by CTNNA1 overexpression plasmid transfection. Cell proliferation, apoptosis, migration and invasion were respectively assessed by CCK-8 assay, flow cytometry, wound healing assay and transwell assay. The expression levels of epithelial–mesenchymal transition (EMT)-related factors were tested by qRT-PCR and Western blot. BLCA nude mice models were constructed to explore the effects of CTNNA1 on BLCA in vivo. Gene set enrichment analysis (GSEA) was proceeded to identify the CTNNA1-related pathways in BLCA. Results The expressions of CTNNA1 were down-regulated in BLCA tissues and cell lines, and its low expression indicated poor prognosis of BLCA patients. CTNNA1 inhibited cell proliferation, migration, invasion and EMT and promoted cell apoptosis in BLCA cells. CTNNA1 enhanced E-cadherin expression and suppressed N-cadherin, snail, MMP2 and MMP9 expressions in BLCA cells, which suggested that CTNNA1 repressed EMT in BLCA cells. Moreover, CTNNA1 could inhibit tumor growth in vivo. CTNNA1 was positively associated with P53 and apoptosis pathways in BLCA cells. Conclusion CTNNA1 inhibited cell proliferation, migration, invasion and EMT and promoted cell apoptosis in BLCA via activating P53 and apoptosis pathways. CTNNA1 might be a novel target in BLCA therapy.

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“…As described by early cohort studies ([ 12 , 13 , 14 ], reviewed in [ 8 , 15 ]), the most commonly altered driver mutations in ILC are in CDH1 , TP53 , PIK3CA , FOXA1 , PTEN , TBX3 , FGFR2 , ERBB2 , and ERBB3 . AKT1 and CTNNA1 are increasingly important in ILC [ 16 , 17 ]; however, relatively low mutation frequencies were detected when profiled. These data are presented in Table 1 and Figure 1 , and together with detailed clinicopathologic information in Table S1 .…”

Section: Resultsmentioning

confidence: 99%

The Genomic Landscape of Lobular Breast Cancer

Reed

Foong

Kutasovic

et al. 2021

Cancers

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Invasive lobular carcinoma (ILC) is the second most common breast cancer histologic subtype, accounting for approximately 15% of all breast cancers. It is only recently that its unique biology has been assessed in high resolution. Here, we present a meta-analysis of ILC sequencing datasets, to provide a long-awaited ILC-specific resource, and to confirm the prognostic value and strength of association between a number of clinico-pathology features and genomics in this special tumour type. We consider panel (n = 684), whole exome (n = 215) and whole genome sequencing data (n = 48), and review histology of The Cancer Genome Atlas cases to assign grades and determine whether the ILC is of classic type or a variant, such as pleomorphic, prior to performing statistical analyses. We demonstrate evidence of considerable genomic heterogeneity underlying a broadly homogeneous tumour type (typically grade 2, estrogen receptor (ER)-positive); with genomes exhibiting few somatic mutations or structural alterations, genomes with a hypermutator phenotype, and tumours with highly rearranged genomes. We show that while CDH1 (E-cadherin) and PIK3CA mutations do not significantly impact survival, overall survival is significantly poorer for patients with a higher tumour mutation burden; this is also true for grade 3 tumours, and those carrying a somatic TP53 mutation (and these cases were more likely to be ER-negative). Taken together, we have compiled a meta-dataset of ILC with molecular profiling, and our analyses show that the genomic landscape significantly impacts the tumour’s variable natural history and overall survival of ILC patients.

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αE‐catenin is a candidate tumor suppressor for the development of E‐cadherin‐expressing lobular‐type breast cancer

Cited by 37 publications

References 41 publications

Clinical implications of CTNNA1 germline mutations in asymptomatic carriers

Clinical implications of CTNNA1 germline mutations in asymptomatic carriers

<p>α-E-Catenin (CTNNA1) Inhibits Cell Proliferation, Invasion and EMT of Bladder Cancer</p>

The Genomic Landscape of Lobular Breast Cancer

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