MAGI-1 expression is decreased in several types of human T-cell leukemia cell lines, including adult T-cell leukemia
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Membrane-associated guanylate kinase with inverted orientation protein 1 (MAGI-1) is a cytoplasmic scaffold protein that interacts with various signaling molecules; it negatively controls the cell growth of various types of cells and positively controls cell–cell interaction. In T cells, MAGI-1 has been shown to inhibit Akt activity through its interaction with PTEN and MEK1. In this study we found that MAGI-1 expression is decreased in multiple (9 out of 15) human T-cell leukemia cell lines, including adult T-cell leukemia (ATL), T-cell acute lymphoblastic leukemia and chronic T-cell lymphocytic leukemia. The overexpression of MAGI-1 protein in a MAGI-1-low ATL cell line reduced cellular growth. While the overexpression of MAGI-1 protein in a MAGI-1-low ATL cell line reduced the Akt and MEK activities, the knockdown of MAGI-1 in a MAGI-1-high ATL cell line augmented the Akt and MEK activities. Collectively, the findings of the present study suggest that the decreased expression of MAGI-1 in human T cells contributes to the development of several types of T-cell leukemia, partly through the stimulation of the Akt and MEK pathways.
KeywordsT-cell leukemia ATL MAGI-1 Akt MEK1/2
The authors thank Hiroyuki Miyoshi and Yasuaki Yamada for providing us with the lentiviral vector system and ATL cell lines, respectively. We thank Takeda Pharmaceutical Company for providing recombinant human IL-2. We also express our gratitude to Misako Tobimatsu for providing technical assistance. This work was supported in part by a grant-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
Compliance with ethical standards
Funding was supported by JSPS KAKENHI Grant Numbers (15H04704, 16K15502).
Conflict of interest
The authors declare no conflicts of interest.
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