TITLE:
Meis1 Is Required for c-Met Inhibition to Suppress Cell Proliferation of Skin Squamous Cell Carcinoma Cells
AUTHORS:
Megumi Saito, Kazuhiro Okumura, Yasuhiro Yoshizawa, Haruka Munakata, Eriko Isogai, Yuichi Wakabayashi
KEYWORDS:
Meis1, c-Met, Skin Squamous Cell Carcinoma
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.4 No.7,
July
11,
2016
ABSTRACT: Previous
studies have shown that Meis1 plays an important role in the pathogenesis of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Meis1 belongs
to the TALE family, the members of which are used as biomarkers for AML. Meis1 has
been shown to play a functional role in epithelial tissues, such as skin. However,
its functions in skin carcinogenesis remain poorly understood. On the other hand, the c-Met inhibitor SU11274 has been identified
through drug screening with HOXA9/Meis1-induced AML cell lines. SU11274 altered
cell proliferation and the cell cycle status in human AML cell lines. Thus, we hypothesized
that the effects of SU11274 are dependent on Meis1 and that its knockdown may diminish
the effects of SU11274 not only in AML cell lines, but also in skin cancer cell
lines. In order to test our hypothesis, we established Meis1 knockdown cell lines
using two skin squamous cell carcinoma cell lines (B9 and D3) and treated these
cell lines with SU11274. The results obtained showed that SU11274 suppressed cell
proliferation by modulating cell cycle progression in the presence of Meis1, but
not in its absence. Furthermore, an expression
analysis showed that SU11274 activated the transcription of Meis1, which
led to the transcription of Hif1α and
Cdkn2a (p16Ink4a and p19Arf). These results suggest that Meis1 is required for the
c-Met inhibitor SU11274 to suppress the proliferation of the skin squamous cell
carcinoma cell lines.