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.
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