Decreased expression of CADM1 and CADM4 are associated with advanced stage breast cancer

Saito, Motonobu; Goto, Akiteru; Abe, Noriko; Maeda, Daichi; Ohtake, Tohru; Murakami, Yoshinori; Takenoshita, Seiichi

doi:10.3892/ol.2017.7536

Cited by 18 publications

(26 citation statements)

References 22 publications

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“…CADM1 is frequently lost in invasive lung adenocarcinoma lesions when compared with those non‑invasive lung adenocarcinoma lesions 5. In recent years, accumulated evidences have confirmed that CADM1 is always inactivated in breast cancer, and its inactivation closely associated with patients’ poor prognosis and advanced progression 6–8. For example, a study published by Saito et al8 reported that 76.9% (160/208) of primary invasive breast cancer tissues showed CADM1 negative expression, and lack of CADM1 expression in these cases was associated with advanced tumor stage, suggesting a vital role of CADM1 plays in breast cancer.…”

Section: Introductionmentioning

confidence: 99%

<p>MicroRNA-155-3p promotes breast cancer progression through down-regulating CADM1</p>

Zhang¹,

Zhong²,

Luo³

et al. 2019

OTT

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Background/purposeCell adhesion molecule 1 (CADM1) functions as a tumor suppressor and has been identified to be frequently inactivated in breast cancer, and closely associated with patients’ poor prognosis and advanced TNM stage. However, the mechanisms underlying CADM1 in breast cancer progression remains incompletely clear. miR-155, a predicted modulator of CADM1 was reported to be overexpressed in breast cancer, and its high expression level was closely related to the malignant progression of breast cancer. The present study aimed to explore whether miR-155-3p could modulate CADM1 expression and then involved in the progression of breast cancer.MethodsThe expression patterns of miR-155-3p in breast cancer tissues and cell lines were determined by RT-PCR technology. The relationship between CADM1 and miR-155-3p were determined by the luciferase gene reporter and Western Blot (WB) assays. Cell proliferation, apoptosis rates and tumorigenesis were determined by CCK-8, flow cytometry and in vivo xenotransplanation experiments, respectively.ResultsmiR-155-3p was up-regulated in breast cancer tissues and cells when compared to the adjacent normal tissues and normal breast MCF 10A cells. The mRNA and protein levels of CADM1 showed opposite expression patterns to that of miR-155-3p expression detected, and miR-155-3p could negatively regulate CADM1 expression in breast cancer MCF-7 cells. Moreover, gain-of function assay showed that overexpression of miR-155-3p promoted cell proliferation, tumorigenesis and repressed cell apoptosis, but these effects were all significantly impaired when the cells were simultaneously transfected with OE-CADM1, the overexpressing vector of CADM1.ConclusionThis study revealed that miR-155-3p could accelerate the progression of breast cancer via down-regulation of CADM1 expression.

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Section: Introductionmentioning

confidence: 99%

<p>MicroRNA-155-3p promotes breast cancer progression through down-regulating CADM1</p>

Zhang¹,

Zhong²,

Luo³

et al. 2019

OTT

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“…CADM1, a member of the cell adhesion molecule family, has been proven to be a tumor suppressor in many cancers, including breast cancer (15), esophageal squamous cell carcinoma (16), and hepatocellular carcinoma (17). In MM, it was reported that the expression of CADM1 was also significantly downregulated and functions as a tumor suppressor by suppressing matrix metalloproteinases (MMPs) in MM (18, 19).…”

Section: Introductionmentioning

confidence: 99%

LNMAT1 Promotes Invasion-Metastasis Cascade in Malignant Melanoma by Epigenetically Suppressing CADM1 Expression

Mou

Zhang

et al. 2019

Front. Oncol.

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The invasion-metastasis cascade is one of the most important factors relating to poor survival and prognosis of malignant melanoma (MM) patients. Long non-coding RNA lymph node metastasis associated transcript 1 (LNMAT1) is a key regulator in lymph node metastasis of multiple cancer types, but the roles and underlying mechanisms of LNMAT1 in the invasion-metastasis cascade of MM remain unclear. In the present study, we aimed to investigate the expression and function of LNMAT1 in MM. Here, we found that LNMAT1 was upregulated in MM tissues and cells, and its expression levels were further enhanced in MM patients with lymph node metastasis and metastatic MM cells. Using loss-of-function assays, we found that LNMAT1 promoted cell migration and invasion and lung metastasis in MM in vitro and in vivo. Moreover, we found that cell adhesion molecule 1 (CADM1), the established tumor suppressor in MM, was the downstream target of LNMAT1. Mechanistically, LNMAT1 epigenetically suppressed CADM1 expression by recruiting EZH2, the key regulator of trimethylation of histone H3 at lysine 27 (H3K27me3), to the CADM1 promoter, resulting in transcriptional inhibition of CADM1. Lastly, rescue assays demonstrated that LNMAT1 promoted cell migration and invasion of MM by suppressing CADM1 expression. Our findings elucidate a new mechanism for LNMAT1-mediated invasion-metastasis cascade in MM and suggest that LNMAT1 may be a new therapeutic target and prognostic predictor for MM.

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“…Therefore, it is considered that CADM1 and CADM4 suppress tumor development in cases of breast cancer. However, we previously evaluated CADM1 and CADM4 expression in breast cancer and found that those expression levels were less frequently decreased in TNBC cases than in non-TNBC cases (20). In the present study, we investigated further into CADM1 and CADM4 expression levels in both CNB and surgical specimens in TNBC patients who received PST.…”

Section: Discussionmentioning

confidence: 99%

“…IHC staining for CADM1 and CADM4 was performed by same method as previously described (20). The breast cancer tissue samples were fixed in 10% formalin, embedded in paraffin, cut into 4-µm sections and stained with hematoxylin and eosin (H&E) and other primary antibodies.…”

Section: Methodsmentioning

confidence: 99%

“…CADM4 , which is located on chromosome 19q13.31, also works as a tumor suppressor gene in renal clear cell carcinoma, colon cancer, and breast cancer (17–19). We recently demonstrated that CADM1 and CADM4 were less frequently inactivated in TNBC than in non-TNBC (20). Our results that the roles of CADM1 and CADM4 in TNBC are different than their in non-TNBC, and those genes may therefore be associated with the therapeutic response to PST for TNBC.…”

Section: Introductionmentioning

confidence: 99%

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Expression profile of CADM1 and CADM4 in triple negative breast cancer with primary systemic therapy

et al. 2018

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Triple negative breast cancer (TNBC) is defined by a lack of ER, PgR, and HER2 expression, and to date there have been no significant advances in treatment by targeted therapies against those molecules. Therefore, primary systemic therapy (PST) followed by surgery is the standard therapy for patients with advanced TNBC. According to gene expression analysis, TNBC has a distinct profile when compared with non-TNBC, suggesting that a unique gene affects the treatment efficacy of PST. Cell adhesion molecule (CADM) genes encode an immunoglobulin superfamily molecule involved in cell-to-cell adhesion in a variety of human epithelial cells. While it has been reported that inactivation of CADM1 and CADM4 serves a pivotal role in the progression of breast cancer, a full analysis has not been completed for TNBC. Previous studies have reported that CADM1 and CADM4 expression is less likely to be decreased in TNBC than in non-TNBC. In the present study, CADM1 and CADM4 expression was evaluated in patients with TNBC who had received PST. The present study revealed that loss or weak expression of CADM1 was frequently observed in non-pathological complete response patients. Furthermore, while the majority of TNBC cases exhibited high CADM1 expression, a small number of cases exhibited low CADM1 expression and low therapeutic response of PST for TNBC. These results suggest that CADM1 has a pivotal role in anti-PST efficacy in patients with TNBC.

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Decreased expression of CADM1 and CADM4 are associated with advanced stage breast cancer

Cited by 18 publications

References 22 publications

<p>MicroRNA-155-3p promotes breast cancer progression through down-regulating CADM1</p>

<p>MicroRNA-155-3p promotes breast cancer progression through down-regulating CADM1</p>

LNMAT1 Promotes Invasion-Metastasis Cascade in Malignant Melanoma by Epigenetically Suppressing CADM1 Expression

Expression profile of CADM1 and CADM4 in triple negative breast cancer with primary systemic therapy

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