Comprehensive functional characterization of cancer–testis antigens defines obligate participation in multiple hallmarks of cancer

  title={Comprehensive functional characterization of cancer–testis antigens defines obligate participation in multiple hallmarks of cancer},
  author={Kimberly E. Maxfield and Patrick J. Taus and Kathleen Corcoran and Joshua S. Wooten and Jennifer Macion and Yunyun Zhou and Mark D. Borromeo and Rahul K. Kollipara and Jingsheng Yan and Yang Xie and Xian-Jin Xie and Angelique W Whitehurst},
  journal={Nature Communications},
Tumours frequently activate genes whose expression is otherwise biased to the testis, collectively known as cancer–testis antigens (CTAs). The extent to which CTA expression represents epiphenomena or confers tumorigenic traits is unknown. In this study, to address this, we implemented a multidimensional functional genomics approach that incorporates 7 different phenotypic assays in 11 distinct disease settings. We identify 26 CTAs that are essential for tumor cell viability and/or are… 
HORMAD1 Is a Negative Prognostic Indicator in Lung Adenocarcinoma and Specifies Resistance to Oxidative and Genotoxic Stress.
Results suggest that HORMAD1 expression specifies a novel subtype of LUAD, which has adapted to mitigate DNA damage, and could represent a direct target for intervention to enhance sensitivity to DNA-damaging agents or as an immunotherapeutic target in patients.
Functional characterisation of SPO11 in human cancer cells
It is demonstrated that human SPO11 protein is observed in testis, most cancer cells, and some tumour tissues, but it is not found in normal healthy tissues, and evidence is presented to suggest that SPO 11 depletion alters the level of cell cycle regulatory proteins without inducing apoptosis or senescence, suggestingSPO11 functions in cancer cells to alter cell cycle dynamics.
The testis protein ZNF165 is a SMAD3 cofactor that coordinates oncogenic TGFβ signaling in triple-negative breast cancer
It is reported that ZNF165, a CT antigen frequently expressed in triple-negative breast cancer (TNBC), associates with SMAD3 to modulate transcription of transforming growth factor β (TGFβ)-dependent genes and thereby promote growth and survival.
Emerging roles of cancer-testis antigenes, semenogelin 1 and 2, in neoplastic cells
The role of SEMGs in the reproductive system is highlighted and the data on their expression and functions in malignant cells of various origins is summarized.
Context-Dependent Tumorigenic Effect of Testis-Specific Mitochondrial Protein Tiny Tim 2 in Drosophila Somatic Epithelia
It is shown that in the larval neuroepithelium, ectopic expression of the germline-specific component of the inner mitochondrial translocation complex tiny tim 2 (ttm2) brings about cell autonomous hyperplasia and extension of G2 phase and that a unique tumorigenic event may trigger different tumor growth pathways depending on the tissular context.
Role and Clinical Utility of Cancer/Testis Antigens in Head and Neck Squamous Cell Carcinoma
Cancer/testis antigens hold intriguing potential as therapeutic targets and as biomarkers for prognosis and that they can provide novel insights into oncogenic mechanisms, their further study in the context of head and squamous cell carcinoma is warranted.
Meiosis-like Functions in Oncogenesis: A New View of Cancer.
It is postulate that some meiotic chromosome-regulatory functions contribute to a soma-to-germline model for cancer, in which activation of germline functions drive oncogenesis, and it is extended to propose that meiotic factors could be powerful sources of targets for therapeutics and biomonitoring in oncology.


Multiple Cancer Testis Antigens Function To Support Tumor Cell Mitotic Fidelity
It is demonstrated that combining paclitaxel with a small-molecule inhibitor of the gametogenic and tumor cell mitotic protein TACC3 leads to enhanced centrosomal abnormalities, activation of death programs, and loss of anchorage-independent growth.
Cause and consequence of cancer/testis antigen activation in cancer.
The history of the CTA field is reviewed and recent findings indicating that CTAs can play functional roles in supporting tumorigenesis are presented.
Synthetic lethal screen identification of chemosensitizer loci in cancer cells
It is shown that several of these targets sensitize lung cancer cells to paclitaxel concentrations 1,000-fold lower than otherwise required for a significant response, and mechanistic relationships between cancer-associated aberrant gene expression programmes and the basic cellular machinery required for robust mitotic progression are identified.
Cancer/testis antigens, gametogenesis and cancer
CT antigens are being evaluated for their role in oncogenesis — recapitulation of portions of the germline gene-expression programme might contribute characteristic features to the neoplastic phenotype, including immortality, invasiveness, immune evasion, hypomethylation and metastatic capacity.
MYC is activated by USP2a-mediated modulation of microRNAs in prostate cancer.
A new mechanism by which USP2a enhances MYC levels through the modulation of specific subsets of microRNAs in prostate cancer, suggesting alternative therapeutic strategies for targeting MYC is highlighted.
Cancer/testis (CT) antigens - a new link between gametogenesis and cancer.
  • L. Old
  • Biology
    Cancer immunity
  • 2001
As a consequence of T cell epitope cloning and SEREX analysis, a growing number of CT antigens have now been defined, and other approaches, e.g., representational difference analysis and in silico surveys of cDNA data banks are adding to the list.
Quantitative Proteomic Profiling Identifies DPYSL3 as Pancreatic Ductal Adenocarcinoma-Associated Molecule That Regulates Cell Adhesion and Migration by Stabilization of Focal Adhesion Complex
Results indicate successful application of combined proteomic approaches to identify a novel key player, dihydropyrimidinase-like 3, in pancreatic ductal adenocarcinoma tumorigenesis, which may serve as an important biomarker and/or drug target to improve therapeutic strategies.
CTdatabase: a knowledge-base of high-throughput and curated data on cancer-testis antigens
The database presented here, CTdatabase, is more than a repository of CT antigen data, since all the available information was carefully curated and annotated with most data being specifically processed for CT antigens and stored locally.
Comprehensive molecular portraits of human breast tumors
The ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity.
Zinc-finger protein ZNF165 is a novel cancer-testis antigen capable of eliciting antibody response in hepatocellular carcinoma patients
Results suggest that ZNF165, a member of the ZNF family, is a novel CT antigen capable of eliciting humoral immune response and be involved in tumour biology.