Small breast epithelial mucin promotes the invasion and metastasis of breast cancer cells via promoting epithelial‑to‑mesenchymal transition

Li, Qiu‐Hua; Liu, Zhao‐Zhe; Ge, Yanan; Xing, Lingxiao; Xie, Xiaodong; Zheng, Zhendong; Ma, Yue‐Hai; Liu, Bin

doi:10.3892/or.2020.7640

Cited by 19 publications

(13 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study, it was found that MUCL1 silencing inhibited EMT phenomenon, as evidenced by increased E-cadherin and decreased vimentin expression levels. Consistent with the aforementioned finding, it was previously reported that knockdown of MUCL1 in breast cancer cells inhibits EMT ( 17 ). The mucin proteins, specifically MUC1, have been shown to play a key role in tumorigenesis by integrating EMT program ( 35 ).…”

Section: Discussionsupporting

confidence: 88%

“…MUCL1 has been extensively studied in breast cancer mostly as a diagnostic biomarker for micrometastasis (10)(11)(12)(13). The therapeutic role of MUCL1 targeting in breast cancer has been previously reported (17). Conley et al (28) reported that Her2 drives MUCL1 expression and regulates cell proliferation in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

“…MUCL1-silenced HT-29 and SW620 cells showed inhibition in the number of invasive cells compared with control siRNA cells, which exhibited significantly higher invasion ability. Li et al ( 17 ) showed that knockdown of MUCL1 in MCF7 and MDA-MB-231 inhibited the invasion and migration.…”

Section: Discussionmentioning

confidence: 99%

“…Liu et al ( 16 ) detected SBEM expression in breast tumor tissues and blood samples and proposes it as a marker for predicting hematogenous micrometastasis and neoadjuvant chemotherapy response in breast cancer. Recently, Li et al ( 17 ) described the role of SBEM in promoting invasion and metastasis by inducing EMT in breast cancer cells. To the best of our knowledge, the association between MUCL1 expression and its function in CRC is still largely unknown.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Targeting MUCL1 protein inhibits cell proliferation and EMT by deregulating β‑catenin and increases irinotecan sensitivity in colorectal cancer

et al. 2022

View full text Add to dashboard Cite

With >1.85 million cases and 850,000 deaths annually, colorectal cancer (CRC) is the third most common cancer detected globally. CRC is an aggressive malignancy with metastasis and, in spite of advances in improved treatment regimen, distant disease failure rates remain disappointingly high. Mucin-like 1 (MUCL1) is a small glycoprotein highly expressed mainly in breast cancer. The involvement of the MUCL1 protein in CRC progression and the underlying mechanism have been largely unknown. The aim of the present study was to investigate the MUCL1 expression profile and its functional significance in CRC. The Cancer Genome Atlas dataset revealed that MUCL1 expression was higher in colorectal tumor compared with normal tissues. MUCL1 was also revealed to be expressed in human CRC cell lines. The results demonstrated that MUCL1 promoted cell proliferation and colony formation, confirming its oncogenic potential. Silencing MUCL1 with short interfering RNA inhibited the protein expression of Bcl2 family proteins, such as Bcl2 and BclxL. Targeting MUCL1 resulted in significant inhibition in cell invasive and migratory behavior of HT-29 and SW620 cells. In addition, the expression of E-cadherin increased whereas the expression of vimentin decreased in MUCL1-silenced cells, confirming inhibition of epithelial-mesenchymal transition (EMT) process. Thus, it was revealed that MUCL1 plays a notable role in cell invasion and migration by inhibiting EMT in CRC. Mechanistically, MUCL1 drives β-catenin activation by Ser-552 phosphorylation, nuclear accumulation and transcriptional activation. Targeting MUCL1 increases the drug sensitivity of CRC cells towards irinotecan. These findings thus demonstrated that MUCL1 acts as a modifier of other pathways that play an important role in CRC progression and MUCL1 was identified as a potential target for CRC therapeutics.

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Targeting MUCL1 protein inhibits cell proliferation and EMT by deregulating β‑catenin and increases irinotecan sensitivity in colorectal cancer

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Meanwhile, downregulation of epithelial markers (E‐cadherin, ZO‐1, etc. ), upregulation of mesenchymal markers including N‐cadherin, Vimentin, Twist, and Snail are associated with increased migration ability 13,14 . Liu et al 14 identified that 1.4 dyne/cm 2 FSS contributed to cancer cell migration by inducing the occurrence of EMT in laryngeal squamous carcinoma Hep‐2 cells.…”

Section: Introductionmentioning

confidence: 99%

Autophagy modulates FSS‐induced epithelial–mesenchymal transition in hepatocellular carcinoma cells

Tian

Pei

et al. 2021

Molecular Carcinogenesis

View full text Add to dashboard Cite

Hepatocellular carcinoma is a highly fatal disease and threatens human health seriously. Fluid shear stress (FSS), which is caused by the leakage of plasma from abnormally permeable tumor blood vessels and insufficient lymphatic drainage, has been identified as contributing pathologically to cancer metastasis. Autophagy and epithelial–mesenchymal transition (EMT) are both reported to be involved in cancer cell migration and invasion, but little has been revealed about the interaction between autophagy and EMT under a tumor mechanical microenvironment. Here, we identified that exposure to 1.4 dyne/cm2 FSS could promote the formation of autophagosomes and significantly increase the expressions of autophagy‐related markers of beclin1 and ATG7, and the ratio of LC3Ⅱ/Ⅰ in both of HepG2 and QGY‐7703 cells. The FSS loading also elevated the levels of mesenchymal markers N‐cadherin, Vimentin, Twist, Snail, and β‐catenin, while the epithelial markers E‐cadherin showed a decrease. Once the autophagy was blocked by 3‐methyladenine (3‐MA) or knocking ATG5 down, the occurrence of FSS‐induced EMT was inhibited dramatically according to the expression and translocation of E‐cadherin, N‐cadherin, and β‐catenin. Given the effect of EMT on cell migration, we observed that inhibition of autophagy could impede FSS‐induced cell migration. Collectively, this study demonstrated that autophagy played a crucial role in FSS‐induced EMT and cell migration in hepatocellular carcinoma.

show abstract

The analysis of transcriptomic signature of TNBC—searching for the potential RNA-based predictive biomarkers to determine the chemotherapy sensitivity

Supplitt,

Karpinski,

Sasiadek

et al. 2024

J Appl Genetics

View full text Add to dashboard Cite

Neoadjuvant chemotherapy is the foundation treatment for triple-negative breast cancer (TNBC) and frequently results in pathological complete response (pCR). However, there are large differences in clinical response and survival after neoadjuvant chemotherapy of TNBC patients. The aim was to identify genes whose expression significantly associates with the efficacy of neoadjuvant chemotherapy in patients with TNBC. Transcriptomes of 46 formalin-fixed paraffin-embedded (FFPE) tumor samples from TNBC patients were analyzed by RNA-seq by comparing 26 TNBCs with pCR versus 20 TNBCs with pathological partial remission (pPR). Subsequently, we narrowed down the list of genes to those that strongly correlated with drug sensitivity of 63 breast cancer cell lines based on Dependency Map Consortium data re-analysis. Furthermore, the list of genes was limited to those presenting specific expression in breast tumor cells as revealed in three large published single-cell RNA-seq breast cancer datasets. Finally, we analyzed which of the selected genes were significantly associated with overall survival (OS) in TNBC TCGA dataset. A total of 105 genes were significantly differentially expressed in comparison between pPR versus pCR. As revealed by PLSR analysis in breast cancer cell lines, out of 105 deregulated genes, 42 were associated with sensitivity to docetaxel, doxorubicin, paclitaxel, and/or cyclophosphamide. We found that 24 out of 42 sensitivity-associated genes displayed intermediate or strong expression in breast malignant cells using single-cell RNAseq re-analysis. Finally, 10 out of 24 genes were significantly associated with overall survival in TNBC TCGA dataset. Our RNA-seq-based findings suggest that there might be transcriptomic signature consisted of 24 genes specifically expressed in tumor malignant cells for predicting neoadjuvant response in FFPE samples from TNBC patients prior to treatment initiation. Additionally, nine out of 24 genes were potential survival predictors in TNBC. This group of 24 genes should be further investigated for its potential to be translated into a predictive test(s).

show abstract

Small breast epithelial mucin promotes the invasion and metastasis of breast cancer cells via promoting epithelial‑to‑mesenchymal transition

Cited by 19 publications

References 40 publications

Targeting MUCL1 protein inhibits cell proliferation and EMT by deregulating β‑catenin and increases irinotecan sensitivity in colorectal cancer

Targeting MUCL1 protein inhibits cell proliferation and EMT by deregulating β‑catenin and increases irinotecan sensitivity in colorectal cancer

Autophagy modulates FSS‐induced epithelial–mesenchymal transition in hepatocellular carcinoma cells

The analysis of transcriptomic signature of TNBC—searching for the potential RNA-based predictive biomarkers to determine the chemotherapy sensitivity

Contact Info

Product

Resources

About