MUC1c Regulates Cell Survival in Pancreatic Cancer by Preventing Lysosomal Permeabilization

Banerjee, Sulagna; Mujumdar, Nameeta; Dudeja, Vikas; MacKenzie, Tiffany N.; Krosch, Tara Kendall; Sangwan, Veena; Vickers, Selwyn M.; Saluja, Ashok K.

doi:10.1371/journal.pone.0043020

Cited by 21 publications

(16 citation statements)

References 60 publications

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“…MUC1-C–induced transcriptional programs have also been shown to be associated with tumorigenesis and predict a poor outcome in breast and lung cancer patients (Lacunza et al, 2010; MacDermed et al, 2010; Pitroda et al, 2009). The MUC1-C oncoprotein has also been shown to confer androgen-independent growth in human prostate cancer cells and to regulate survival of pancreatic cancer cells (Banerjee et al, 2012) and enhance invasiveness of pancreatic cancer cells by inducing EMT (Roy et al, 2011). …”

Section: Vaccine Targets Involved In Tumor Progression and Drug Resismentioning

confidence: 99%

Therapeutic Cancer Vaccines

Schlom

Hodge

Palena

et al. 2014

Advances in Cancer Research

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Therapeutic cancer vaccines have the potential of being integrated in the therapy of numerous cancer types and stages. The wide spectrum of vaccine platforms and vaccine targets is reviewed along with the potential for development of vaccines to target cancer cell "stemness," the epithelial-to-mesenchymal transition (EMT) phenotype, and drug-resistant populations. Preclinical and recent clinical studies are now revealing how vaccines can optimally be used with other immune-based therapies such as checkpoint inhibitors, and so-called nonimmune-based therapeutics, radiation, hormonal therapy, and certain small molecule targeted therapies; it is now being revealed that many of these traditional therapies can lyse tumor cells in a manner as to further potentiate the host immune response, alter the phenotype of nonlysed tumor cells to render them more susceptible to T-cell lysis, and/or shift the balance of effector:regulatory cells in a manner to enhance vaccine efficacy. The importance of the tumor microenvironment, the appropriate patient population, and clinical trial endpoints is also discussed in the context of optimizing patient benefit from vaccine-mediated therapy.

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Section: Vaccine Targets Involved In Tumor Progression and Drug Resismentioning

confidence: 99%

Therapeutic Cancer Vaccines

Schlom

Hodge

Palena

et al. 2014

Advances in Cancer Research

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show abstract

“…The androgen receptor has been shown to regulate the MUC1-C oncoprotein expression in human prostate cancer cells [46], while the MUC1-C oncoprotein has been shown to confer androgen-independent growth in human prostate cancer cells [47]. MUC1-C has also been shown to regulate survival of pancreatic cancer cells [48] and enhance invasiveness of pancreatic cancer cells by inducing EMT [49]. …”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of agonist epitopes of the MUC1-C oncoprotein

Jochéms

Tucker

Vergati

et al. 2013

Cancer Immunol Immunother

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The MUC1 tumor-associated antigen is overexpressed in the majority of human carcinomas and several hematologic malignancies. Much attention has been paid to the hypoglycosylated VNTR region of the N-terminus of MUC1 as a vaccine target, and recombinant viral vector vaccines are also being evaluated that express the entire MUC1 transgene. While previous studies have described MUC1 as a tumor-associated tissue differentiation antigen, studies have now determined that the C-terminus of MUC1 (MUC1-C) is an oncoprotein, and its expression is an indication of poor prognosis in numerous tumor types. We report here the identification of 9 potential CD8+ cytotoxic T lymphocyte epitopes of MUC1: 7 in the C-terminus and 2 in the VNTR region, and have identified enhancer agonist peptides for each of these epitopes. These epitopes span HLA-A2, A3, and A24 MHC class I alleles, which encompass the majority of the population. The agonist peptides, compared to the native peptides, more efficiently (a) generate T-cell lines from the peripheral blood mononuclear cells of cancer patients, (b) enhance the production of IFN-γ by peptide-activated human T cells, and (c) lyse human tumor cell targets in an MHC-restricted manner. The agonist epitopes described here can be incorporated into various vaccine platforms and for the ex vivo generation of human T cells. These studies provide the rationale for the T-cell–mediated targeting of the oncogenic C-terminus of MUC1, which has been shown to be an important factor in both drug resistance and poor prognosis for numerous tumor types.

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“…The mice were treated with GO-201 (30 mg/kg body weight i.p. ), once a day throughout the graviditas period [Banerjee et al 2012]. Wild-type mice were treated with vehicle only (saline).…”

Section: Muc1 Inhibitor Treatmentmentioning

confidence: 99%