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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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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Microenvironmental regulation of cancer development
TL;DR: This work has shown that Paracrine signaling between epithelial and stromal cells is important for the regulation of the proliferation, invasive, angiogenic, and metastatic behavior of cancer cells.
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A New View into the Regulation of Purine Metabolism: The Purinosome
TL;DR: The purinosome is highlighted as a novel level of metabolic organization of enzymes in cells, its consequences for regulation of Purine metabolism, and the extent that purine metabolism is being targeted for the treatment of cancers.
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TL;DR: Current advances in the understanding of mammalian target of rapamycin for regulating purinosome formation or purine metabolism in cancers are reviewed and the future prospects for targeting purinosomes to treat cancers are discussed.
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Actinin-4 increases cell motility and promotes lymph node metastasis of colorectal cancer.
Kazufumi Honda,Tesshi Yamada,Yasuharu Hayashida,Masashi Idogawa,Satoshi Sato,Fumio Hasegawa,Yoshinori Ino,Masaya Ono,Setsuo Hirohashi +8 more
TL;DR: Actinin-4 actively increases cell motility and promotes lymph node metastasis of colorectal cancer.