Elutidating the mechanisms to Signal molecular mechanisms that control the growth of leukemia cells

2015 Fiscal Year Final Research Report

• Project/Area Number: 26893292
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Laboratory medicine
• Research Institution: Tokyo University of Technology
• Principal Investigator: OKUHASHI Yuki 東京工科大学, 医療保健学部, 助教 (90734715)
• Project Period (FY): 2014-08-29 – 2016-03-31
• Keywords: 白血病 / シグナル伝達 / siRNA / 臨床血液学

Outline of Final Research Achievements

Although Hedgehog (Hh) and Wnt signaling pathways are known to play a role in cancer cell growth, their specific effects on leukemia cells are not fully understood. To clarify the effects of siRNA-mediated knockdown of GLI1 and Catenin beta 1 (CTNNB1), which respectively mediate Hh and Wnt signaling, on cell proliferation as well as Notch and mTOR signaling were studied in leukemia cell lines.
siRNA-mediated knockdown experiments suggested that Hh and Wnt signaling had insignificant effect on the proliferation of the leukemia cell lines used in this study. In NB4 cells, GLI1 as well as CTNNB1 knockdown increased the level of NOTCH1, the cleaved NOTCH1 fragment, HES1, and phosphorylated mTOR protein.
In this study, we report a novel interaction, namely, the activation of Notch and mTOR signaling by the suppression of Hh and Wnt signaling in NB4 cells. The molecular mechanism and significance of this phenomenon as well as its translation to other cell lines needs further examination.

Free Research Field

病態検査学