Matrix‐Metalloprotease Resistant Mucin‐16 (MUC16) Peptide Mutants Represent a Worse Lung Adenocarcinoma Outcome

Patel, Jay S.; Callahan, Blake M.; Chobrutskiy, Boris I.; Blanck, George

doi:10.1002/prca.201800155

Cited by 8 publications

(7 citation statements)

References 39 publications

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“…These variations are nonsynonymous in nature and may change the structural integrity of the barrier. Several studies have reported on the role of MUC16 in different types of cancers including breast cancer [ 36 , 37 , 38 , 39 , 40 ]. As these alterations are germline variations, we hypothesize that, in breast cells they may have allowed the uptake/release of cell-signaling molecules leading to initiation/blockage of signaling pathways, subsequently triggering tumor development and progression at an early age in these women.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Cohort Analysis of Mutational Spectrum in Early Onset Breast Cancer Patients

Midha

Huang

Yang

et al. 2020

Cancers

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Early onset breast cancer (EOBC), diagnosed at age ~40 or younger, is associated with a poorer prognosis and higher mortality rate compared to breast cancer diagnosed at age 50 or older. EOBC poses a serious threat to public health and requires in-depth investigation. We studied a cohort comprising 90 Taiwanese female patients, aiming to unravel the underlying mechanisms of EOBC etiopathogenesis. Sequence data generated by whole-exome sequencing (WES) and whole-genome sequencing (WGS) from white blood cell (WBC)–tumor pairs were analyzed to identify somatic missense mutations, copy number variations (CNVs) and germline missense mutations. Similar to regular breast cancer, the key somatic mutation-susceptibility genes of EOBC include TP53 (40% prevalence), PIK3CA (37%), GATA3 (17%) and KMT2C (17%), which are frequently reported in breast cancer; however, the structural protein-coding genes MUC17 (19%), FLG (16%) and NEBL (11%) show a significantly higher prevalence in EOBC. Furthermore, the top 2 genes harboring EOBC germline mutations, MUC16 (19%) and KRT18 (19%), encode structural proteins. Compared to conventional breast cancer, an unexpectedly higher number of EOBC susceptibility genes encode structural proteins. We suspect that mutations in structural proteins may increase physical permeability to environmental hormones and carcinogens and cause breast cancer to occur at a young age.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Cohort Analysis of Mutational Spectrum in Early Onset Breast Cancer Patients

Midha

Huang

Yang

et al. 2020

Cancers

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“…The therapeutic monoclonal antibody is generally effective in the extracellular region, and the dissociation of the extracellular region leads to the loss of target; on the other hand, the MUC16 gene fragment is relatively long and has a high mutation rate 37,44 . Some mutant strains can promote MUC16 expression 24 and even have a higher tumorigenic effect than that of the original target change 39,51 . We confirmed that ERO1L was a key factor upstream of MUC16 that significantly affected MUC16 expression.…”

Section: Discussionmentioning

confidence: 99%

ERO1L promotes IL6/sIL6R signaling and regulates MUC16 expression to promote CA125 secretion and the metastasis of lung cancer cells

Lei

Zang

et al. 2020

Cell Death Dis

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The abnormal secretion of CA125, a classic tumor marker, is usually related to a poor prognosis in various tumors. Thus, this study aimed to explore the potential mechanisms that promote CA125 secretion in lung cancer. By querying the database, the gene endoplasmic reticulum oxidoreductase 1L (ERO1L) was identified and chosen as the research subject. The antibody chips were used to screen the lung cancer cell supernatant and found that the most obvious secreted protein was CA125. ERO1L was found to promote the secretion of IL6R by affecting the formation of disulfide bonds. IL6R bound to IL6 and triggered the activation of the NF-κB signaling pathway. Then, NF-κB bound to the promoter of MUC16, resulting in overexpression of MUC16. The extracellular segment of MUC16 was cleaved to form CA125, while the C terminus of MUC16 promoted the EMT phenotype and the release of IL6, forming a positive feedback pathway. In conclusion, ERO1L might affect the secretion of CA125 through the IL6 signaling pathway and form a positive feedback loop to further promote the development of lung cancer. This might expand the application scope of CA125 in lung cancer.

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“…A MUC16-mutant was resistant to matrix-metalloproteases (MMPs) that were released by LUAD cells. Furthermore, LUAD with both MMP-and MUC16-resistant mutant expression had an unfavourable prognosis [45]. e overexpression of MUC16 was correlated with familial lung cancer, air pollution produced by coal indoor, higher metastasis, and an advanced stage.…”

Section: Mucs In Nsclcmentioning

confidence: 98%

Expression of Mucin Family Proteins in Non-Small-Cell Lung Cancer and its Role in Evaluation of Prognosis

Tang

et al. 2022

Journal of Oncology

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Lung cancer is still the major contributor to cancer-related mortality. Over 85% of patients suffer from non-small-cell lung cancer (NSCLC). Mucins (MUCs) are large glycoproteins secreted or membrane-bound produced by epithelial cells in normal and malignant tissues. They are the major components of the mucous gel that covers the surface of the respiratory epithelium. Certain MUCs have been used or proposed to act as biomarkers for lung cancer. Nevertheless, the expression, messenger ribonucleic acid (mRNA) levels, and the prognostic value of MUCs in NSCLC are yet to be investigated systematically. In this research, the biological information of MUC proteins in patients with NSCLC was examined using a series of databases. The results based on gene expression profiling interactive analysis (GEPIA) illustrated that the expression of MUC3A, MUC4, MUC5B, MUC13, MUC16, and MUC21 mRNAs was remarkably upmodulated in lung adenocarcinoma (LUAD) patients, whereas the MUC1 expression was downregulated in lung squamous cell carcinoma (LUSC) patients. Kaplan–Meier plotter (KM Plotter) analysis revealed that elevated mRNA expression levels of MUC3A and MUC16 were linked to unfavourable overall survival (OS) in NSCLC, while increased mRNA expression of MUC1 and MUC15 was linked to good OS, especially in LUAD patients. In addition, differential expression of MUC1, MUC3A/3B, MUC8, MUC12, MUC15, and MUC16 mRNA was linked to the prognoses of NSCLC patients with varied clinical-pathological subtypes. Genetic alterations of MUCs in NSCLC primarily involved mutations, fusion, amplification, deep deletion, and multiple alterations according to cancer genomics (cBioPortal). Therefore, we propose that combinations of MUC proteins can act as prognostic biomarkers and demonstrate the therapeutic potential for NSCLC-related therapy.

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Matrix‐Metalloprotease Resistant Mucin‐16 (MUC16) Peptide Mutants Represent a Worse Lung Adenocarcinoma Outcome

Cited by 8 publications

References 39 publications

Comprehensive Cohort Analysis of Mutational Spectrum in Early Onset Breast Cancer Patients

Comprehensive Cohort Analysis of Mutational Spectrum in Early Onset Breast Cancer Patients

ERO1L promotes IL6/sIL6R signaling and regulates MUC16 expression to promote CA125 secretion and the metastasis of lung cancer cells

Expression of Mucin Family Proteins in Non-Small-Cell Lung Cancer and its Role in Evaluation of Prognosis

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