Chemoresistance Is Associated with MUC1 and Lewis y Antigen Expression in Ovarian Epithelial Cancers

Zhang, Danye; Gao, Jian; Zhu, Li; Hu, Zhenhua; Hou, Rui; Liu, Shuice; Tan, Mingzi; Liu, Juanjuan; Lin, Bei

doi:10.3390/ijms140611024

Cited by 15 publications

(7 citation statements)

References 27 publications

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“…MUC1 protein level is significantly increased in platinum resistant ovarian tumors compared to those in sensitive-group because of chromosomal amplifications of 1q21-q22 [52]. A follow-up analysis of 92 ovarian cancer patient cohort also showed that the increase of MUC1 expression is a significant risk factor for chemoresistance to taxane combined platinum-based drugs in patients with ovarian epithelial cancer [53].…”

Section: Non-mucinous Tumorsmentioning

confidence: 95%

Mucins and tumor resistance to chemotherapeutic drugs

Jonckheere

Skrypek

Seuningen

2014

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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Epithelial cancer patients not considered eligible for surgical resection frequently benefit from chemotherapy. Chemotherapy is the treatment of cancer with one or combination of cytotoxic or cytostatic drugs. Recent advances in chemotherapy allowed a great number of cancer patients to receive treatment with significant results. Unfortunately, resistance to chemotherapeutic drug treatment is a major challenge for clinicians in the majority of epithelial cancers because it is responsible for the inefficiency of therapies. Mucins belong to a heterogeneous group of large O-glycoproteins that can be either secreted or membrane-bound. Implications of mucins have been described in relation to cancer cell behavior and cell signaling pathways associated with epithelial tumorigenesis. Because of the frequent alteration of the pattern of mucin expression in cancers as well as their structural and functional characteristics, mucins are thought to also be involved in response to therapies. In this report, we review the roles of mucins in chemoresistance and the associated underlying molecular mechanisms (physical barrier, resistance to apoptosis, drug metabolism, cell stemness, epithelial-mesenchymal transition) and discuss the therapeutic tools/strategies and/or prognosis biomarkers for personalized chemotherapy that could be proposed from these studies.

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Section: Non-mucinous Tumorsmentioning

confidence: 95%

Mucins and tumor resistance to chemotherapeutic drugs

Jonckheere

Skrypek

Seuningen

2014

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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“…Desmoplastic growth provides tumors a unique environment that favors growth and expansion along with resistance against chemotherapy [95]. Multiple studies suggest a direct role of MUC1 in facilitating desmoplasia and chemoresistance [96–98]. At a metabolic level, MUC1 expression leads to metabolite secretions that are known to facilitate stromal cell metabolism, growth, and/or recruitment.…”

Section: Therapeutic Implications Of the Metabolic Functions Of Muc1mentioning

confidence: 99%

MUC1: A novel metabolic master regulator

Mehla

Singh

2014

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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MUC1, a type I transmembrane protein, is significantly overexpressed and aberrantly glycosylated in tumors of epithelial origin. By virtue of its aberrant signaling due to loss of apical-basal polarity in cancer, MUC1 regulates the metabolite flux at multiple levels. Serving as a transcriptional co-activator, MUC1 directly regulates expression of metabolic genes. By regulating receptor tyrosine kinase signaling, MUC1 facilitates production of biosynthetic intermediates required for cell growth. Also, via direct interactions, MUC1 modulates the activity/stability of enzymes and transcription factors that directly regulate metabolic functions. Additionally, by modulation of autophagy, levels of reactive oxygen species, and metabolite flux, MUC1 facilitates cancer cell survival under hypoxic and nutrient-deprived conditions. This article provides a comprehensive review of recent literature on novel metabolic functions of MUC1.

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“…MUC1‐C, a single‐pass transmembrane protein, can interact with vascular endothelial growth factor (VEGF), early growth factor receptor (EGFR), and others (Kufe, ). The increased expression of MUC1 was a significant risk factor for chemoresistance in ovarian epithelial cancer and contributed to resistance to trastuzumab in breast cancer cells via activation of the HER2 pathway (Raina et al, ; Zhang et al, ). In non‐small cell lung cancers, elevated expression of MUC1 was related with stemness and paclitaxel resistance.…”

Section: Discussionmentioning

confidence: 99%

A five‐gene signature may predict sunitinib sensitivity and serve as prognostic biomarkers for renal cell carcinoma

Chen

et al. 2018

Journal Cellular Physiology

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Sunitinib resistance is, nowadays, the major challenge for advanced renal cell carcinoma patients. Illuminating the potential mechanisms and exploring effective strategies to overcome sunitinib resistance are highly desired. We constructed a reliable gene signature which may function as biomarkers for prediction of sunitinib sensitivity and clinical prognosis. The gene expression profiles were obtained from The Cancer Genome Atlas database. By performing GEO2R analysis, numerous differentially expressed genes (DEGs) were found to be associated with sunitinib resistance. To acquire more precise DEGs, we integrated three different microarray datasets. Functional analysis revealed that these DEGs were mainly involved in Rap1 signaling pathway, p53 signaling pathway and Ras signaling pathway. Then, top five hub genes, BIRC5, CD44, MUC1, TF, CCL5, were identified from protein-protein interaction (PPI) network. Sub-network analysis carried out by MCODE plugin revealed that key DEGs were related with PI3K-Akt signaling pathway, Rap1 signaling pathway and VEGF signaling pathway. Next, we established sunitinib-resistant OS-RC-2 and 786-O cell lines and validated the expression of five hub genes in cell lines. To further evaluate the potentials of five-gene signature for predicting clinical prognosis, we analyzed RCC patients with gene expressions and overall survival information from two independent patient datasets. The Kaplan-Meier estimated the OS of RCC patients in the low- and high-risk groups according to gene expression signature. Multivariate Cox regression analysis indicated that the prognostic power of five-gene signature was independent of clinical features. In conclusion, we developed a five-gene signature which can predict sunitinib sensitivity and OS for advanced RCC patients, providing novel insights into understanding of sunitinib-resistant mechanisms and identification of RCC patients with poor prognosis.

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Chemoresistance Is Associated with MUC1 and Lewis y Antigen Expression in Ovarian Epithelial Cancers

Cited by 15 publications

References 27 publications

Mucins and tumor resistance to chemotherapeutic drugs

Mucins and tumor resistance to chemotherapeutic drugs

MUC1: A novel metabolic master regulator

A five‐gene signature may predict sunitinib sensitivity and serve as prognostic biomarkers for renal cell carcinoma

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