Effect of MUC1 siRNA on Drug Resistance of Gastric Cancer Cells to Trastuzumab

Deng, Min; Jing, Da-Dao; Meng, Xiangjun

doi:10.7314/apjcp.2013.14.1.127

Cited by 21 publications

(18 citation statements)

References 19 publications

(20 reference statements)

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“…There is evidence that resistance to trastuzumab in HER2 positive gastric cancer is mediated through the MUC1 gene, and that silencing the MUC1 gene can reverse resistance to trastuzumab [26]. …”

Section: Prognosis and Treatmentmentioning

confidence: 99%

Mucins in Gastric Cancer - An Update

Boltin¹,

Niv²

2013

J Gastrointest Dig Syst

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Mucins are high-molecular-weight glycoproteins expressed throughout the gastrointestinal tract, with a key role in mucosal protection and function. In gastric cancer expression of MUC5AC and MUC1 is reduced and denovo expression of MUC2 occurs. With progressive loss of tumor differentiation and increased tumor stage, expression of MUC5AC and MUC1 is further reduced, and MUC2 decreases. Isolated MUC2 expression (the intestinal phenotype) correlates with metastatic spread and poor survival. There is emerging evidence that MUC1 acts as an oncoprotein when overexpressed. The cytoplasmic tail of MUC1 interacts with the H. pylori virulence factor cagA and is a major effector of the wnt-β catenin intracellular signalling cascade. Polymorphism in the MUC1 gene has been identified in gastric cancer patients and may have a prospective role in the stratification of high-risk subjects. The MUC1 gene also mediates resistance to the recombinant HER2/neu antibody trastuzumab. Future research efforts will examine targeting MUC1 for therapeutic purposes.

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Section: Prognosis and Treatmentmentioning

confidence: 99%

Mucins in Gastric Cancer - An Update

Boltin¹,

Niv²

2013

J Gastrointest Dig Syst

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show abstract

“…MUC1 has been proposed to be involved in trastuzumab resistance. MUC1 expression levels reportedly affect the antitumor effect of trastuzumab [13,14] and anti-MUC1 antibodies help overcome trastuzumab resistance [15,16]. However, these studies have examined the effect of MUC1 on trastuzumab itself but not on trastuzumabmediated ADCC.…”

Section: Introductionmentioning

confidence: 99%

Anti-KL-6/MUC1 monoclonal antibody reverses resistance to trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity by capping MUC1

et al. 2019

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A B S T R A C TPolymorphic epithelial mucin (MUC1) is generally overexpressed on the surface of most adenocarcinomas including breast cancer. MUC1 is associated with chemotherapeutic resistance and immune evasion of cancer cells; however, the association between MUC1 and trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) remains unclear. In this study, using six breast cancer cell lines with differing expression levels and MUC1 distribution, the present results show that cells with MUC1 overexpression and uniform surface distribution were resistant to trastuzumab-mediated ADCC. Importantly, trastuzumab resistance was reversed upon siRNA-mediated MUC1 knockdown and by using anti-KL-6/MUC1 monoclonal antibody (mAb). Additionally, we visually confirmed that anti-KL-6/MUC1 mAb induced capping of MUC1 molecules on the cell surface, resulting the in death of these cells. These results suggest that not only the quantity but also the cellsurface distribution of MUC1 affects the sensitivity of breast cancer cells to trastuzumab-mediated ADCC.

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“…It is reported that two single nucleotide polymorphisms (rs4072037 and rs2070803) in the MUC1 gene has been identified in gastric cancer patients and may have a prospective role in the stratification of high-risk subjects [171]. The overexpression of MUC1 and MUC4 also mediates resistance to the trastuzumab, a monoclonal antibody against HER-2/neu [172,173] siRNA to MUC1 was tested in trastuzumab drug resistance cells and a better response to the drug was seen in siRNA treated drug resistant cell when compared to control or junk siRNA treatment [174].…”

Section: Stomach Gastric Carcinomamentioning

confidence: 99%

Exploring the role and diversity of mucins in health and disease with special insight into non-communicable diseases

et al. 2015

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Mucins are major glycoprotein components of the mucus that coats the surfaces of cells lining the respiratory, digestive, gastrointestinal and urogenital tracts. They function to protect epithelial cells from infection, dehydration and physical or chemical injury, as well as to aid the passage of materials through a tract i.e., lubrication. They are also implicated in the pathogenesis of benign and malignant diseases of secretory epithelial cells. In Human there are two types of mucins, membrane-bound and secreted that are originated from mucous producing goblet cells localized in the epithelial cell layer or in mucous producing glands and encoded by MUC gene. Mucins belong to a heterogeneous family of high molecular weight proteins composed of a long peptidic chain with a large number of tandem repeats that form the so-called mucin domain. The molecular weight is generally high, ranging between 0.2 and 10 million Dalton and all mucins contain one or more domains which are highly glycosylated. The size and number of repeats vary between mucins and the genetic polymorphism represents number of repeats (VNTR polymorphisms), which means the size of individual mucins can differ substantially between individuals which can be used as markers. In human it is only MUC1 and MUC7 that have mucin domains with less than 40% serine and threonine which in turn could reduce number of PTS domains. Mucins can be considered as powerful two-edged sword, as its normal function protects from unwanted substances and organisms at an arm's length while, malfunction of mucus may be an important factor in human diseases. In this review we have unearthed the current status of different mucin proteins in understanding its role and function in various non-communicable diseases in human with special reference to its organ specific locations. The findings described in this review may be of direct relevance to the major research area in biomedicine with reference to mucin and mucin associated diseases.

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Effect of MUC1 siRNA on Drug Resistance of Gastric Cancer Cells to Trastuzumab

Cited by 21 publications

References 19 publications

Mucins in Gastric Cancer - An Update

Mucins in Gastric Cancer - An Update

Anti-KL-6/MUC1 monoclonal antibody reverses resistance to trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity by capping MUC1

Exploring the role and diversity of mucins in health and disease with special insight into non-communicable diseases

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