Possible Therapeutic Strategy Involving the Purine Synthesis Pathway Regulated by ITK in Tongue Squamous Cell Carcinoma.
Kaoru Onidani,Nami Miura,Yuki Sugiura,Yuichi Abe,Yukio Watabe,Takanori Kakuya,Taisuke Mori,Seiichi Yoshimoto,Jun Adachi,Takao Kiyoi,Yasuaki Kabe,Makoto Suematsu,Takeshi Tomonaga,Takahiko Shibahara,Kazufumi Honda,Kazufumi Honda +15 more
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TLDR
In this paper, the expression of interleukin-2-inducible T-cell kinase (ITK) using immunohistochemistry, and the biological function of ITK was investigated using biochemical, phosphoproteomic, and metabolomic analyses.Abstract:
The epidermal growth factor receptor is the only available tyrosine kinase molecular target for treating oral cancer. To improve the prognosis of tongue squamous cell carcinoma (TSCC) patients, a novel molecular target for tyrosine kinases is thus needed. We examined the expression of interleukin-2-inducible T-cell kinase (ITK) using immunohistochemistry, and the biological function of ITK was investigated using biochemical, phosphoproteomic, and metabolomic analyses. We found that ITK is overexpressed in TSCC patients with poor outcomes. The proliferation of oral cancer cell lines expressing ITK via transfection exhibited significant increases in three-dimensional culture assays and murine inoculation models with athymic male nude mice as compared with mock control cells. Suppressing the kinase activity using chemical inhibitors significantly reduced the increase in cell growth induced by ITK expression. Phosphoproteomic analyses revealed that ITK expression triggered phosphorylation of a novel tyrosine residue in trifunctional purine biosynthetic protein adenosine-3, an enzyme in the purine biosynthesis pathway. A significant increase in de novo biosynthesis of purines was observed in cells expressing ITK, which was abolished by the ITK inhibitor. ITK thus represents a potentially useful target for treating TSCC through modulation of purine biosynthesis.read more
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Materials, workflows and applications of IMAC for phosphoproteome profiling in the recent decade: A review
TL;DR: In this article , a review of the materials, workflows, and applications of IMAC for phosphoproteomic profiling is presented, including a brief discussion on their advantages, current challenges, and trends in the future development.
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RIOK2 Contributes to Cell Growth and Protein Synthesis in Human Oral Squamous Cell Carcinoma
Yusuke Matsuzaki,Yutaka Naito,Nami Miura,Taisuke Mori,Yukio Watabe,Seiichi Yoshimoto,Takahiko Shibahara,Masayuki Takano,Kazufumi Honda +8 more
TL;DR: In this paper , the expression of RIOK2, a key enzyme involved in the maturation steps of the pre-40S ribosomal complex, was significantly associated with poorer overall survival in patients with TSCC.
References
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Qualitatively Different T Cell Phenotypic Responses to IL-2 versus IL-15 Are Unified by Identical Dependences on Receptor Signal Strength and Duration
TL;DR: In this article, the authors performed a quantitative comparison of the phosphotyrosine signaling network and resulting phenotypes triggered by IL-2 and IL-15 and found that the signaling networks activated by IL2 or IL15 are highly similar and that T cell proliferation and metabolism are controlled in a quantitatively distinct manner through IL2/15R signal strength independent of the cytokine identity.
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Inhibition of the IL-2-inducible tyrosine kinase (Itk) activity: a new concept for the therapy of inflammatory skin diseases
Arne von Bonin,Alexandra Rausch,Anne Mengel,Marion Hitchcock,Martin Krüger,Oliver von Ahsen,Claudia Merz,Lars Röse,Christine Stock,Stefan F. Martin,Gabriele Leder,Wolf-Dietrich Döcke,Khusru Asadullah,Ulrich Zügel +13 more
TL;DR: The data reveal that human Itk, comparable to its murine homologue, is expressed mainly in T cells and is increased in lesional skin from patients with atopic dermatitis and allergic contact dermatitis, and represents an interesting new target for the therapy of T‐cell‐mediated inflammatory skin diseases.
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The relevance between the immune response-related gene module and clinical traits in head and neck squamous cell carcinoma
Yidan Song,Yihua Pan,Jun Liu +2 more
TL;DR: The innovative use of a weighted network to analyze HNSCC samples provides new insights into the molecular mechanism and prognosis of HNS CC, and the hub genes identified can be used as biomarkers and therapeutic targets of HnsCC, laying the foundation for the accurate diagnosis and treatment of H NSCC in clinical and research in the future.
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Copy number increase of ACTN4 is a prognostic indicator in salivary gland carcinoma.
Yukio Watabe,Taisuke Mori,Seiichi Yoshimoto,Takeshi Nomura,Takahiko Shibahara,Tesshi Yamada,Kazufumi Honda +6 more
TL;DR: CNI of ACTN4 is a novel indicator for an unfavorable outcome in patients with salivary gland carcinoma, and remains as risk factors for cancer death in multivariate analysis.
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Molecular Characteristics of CTA056, a Novel Interleukin-2-Inducible T-Cell Kinase Inhibitor that Selectively Targets Malignant T Cells and Modulates Oncomirs
Wenchang Guo,Ruiwu Liu,Yoko Ono,Ai Hong Ma,Anthony Martinez,Eduardo Sanchez,Yan Wang,Wenzhe Huang,Anisha Mazloom,Jixian Li,Jinying Ning,Emanual Michael Maverakis,Kit S. Lam,Hsing Jien Kung +13 more
TL;DR: The selective expression and activation of Itk in malignant T cells, as well as the specificity of CTA056 for Itk, make this molecule a potential therapeutic agent for the treatment of T-cell leukemia and lymphoma.