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4. Modulation of Nogo receptor 1 expression orchestrates myelin-associated infiltration of glioblastoma

Author

Hong, Jun-Hee, primary, Kang, Sangjo, additional, Sa, Jason K, additional, Park, Gunwoo, additional, Oh, Young Taek, additional, Kim, Tae Hoon, additional, Yin, Jinlong, additional, Kim, Sung Soo, additional, D’Angelo, Fulvio, additional, Koo, Harim, additional, You, Yeonhee, additional, Park, Saewhan, additional, Kwon, Hyung Joon, additional, Kim, Chan Il, additional, Ryu, Haseo, additional, Lin, Weiwei, additional, Park, Eun Jung, additional, Kim, Youn-Jae, additional, Park, Myung-Jin, additional, Kim, Hyunggee, additional, Kim, Mi-Suk, additional, Chung, Seok, additional, Park, Chul-Kee, additional, Park, Sung-Hye, additional, Kang, Yun Hee, additional, Kim, Jong Heon, additional, Saya, Hideyuki, additional, Nakano, Ichiro, additional, Gwak, Ho-Shin, additional, Yoo, Heon, additional, Lee, Jeongwu, additional, Hur, Eun-Mi, additional, Shi, Bingyang, additional, Nam, Do-Hyun, additional, Iavarone, Antonio, additional, Lee, Seung-Hoon, additional, and Park, Jong Bae, additional

Published
2021
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5. Transglutaminase 2 Inhibition Reverses Mesenchymal Transdifferentiation of Glioma Stem Cells by Regulating C/EBPβ Signaling

Author

Yin, Jinlong, primary, Oh, Young Taek, additional, Kim, Jeong-Yub, additional, Kim, Sung Soo, additional, Choi, Eunji, additional, Kim, Tae Hoon, additional, Hong, Jun Hee, additional, Chang, Nakho, additional, Cho, Hee Jin, additional, Sa, Jason K., additional, Kim, Jeong Cheol, additional, Kwon, Hyung Joon, additional, Park, Saewhan, additional, Lin, Weiwei, additional, Nakano, Ichiro, additional, Gwak, Ho-Shin, additional, Yoo, Heon, additional, Lee, Seung-Hoon, additional, Lee, Jeongwu, additional, Kim, Jong Heon, additional, Kim, Soo-Youl, additional, Nam, Do-Hyun, additional, Park, Myung-Jin, additional, and Park, Jong Bae, additional

Published
2017
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6. Suppression of Glioblastoma Stem Cell Potency and Tumor Growth via LRRK2 Inhibition.

Author

Park S, Kim KH, Bae YH, Oh YT, Shin H, Kwon HJ, Kim CI, Kim SS, Choi HG, Park JB, and Lee BD

Abstract

Leucine-rich repeat kinase 2 (LRRK2), a large GTP-regulated serine/threonine kinase, is well-known for its mutations causing late-onset Parkinson's disease. However, the role of LRRK2 in glioblastoma (GBM) carcinogenesis has not yet been fully elucidated. Here, we discovered that LRRK2 was overexpressed in 40% of GBM patients, according to tissue microarray analysis, and high LRRK2 expression correlated with poor prognosis in GBM patients. LRRK2 and stemness factors were highly expressed in various patient-derived GBM stem cells, which are responsible for GBM initiation. Canonical serum-induced differentiation decreased the expression of both LRRK2 and stemness factors. Given that LRRK2 is a key regulator of glioma stem cell (GSC) stemness, we developed DNK72, a novel LRRK2 kinase inhibitor that penetrates the blood-brain barrier. DNK72 binds to the phosphorylation sites of active LRRK2 and dramatically reduced cell proliferation and stemness factors expression in in vitro studies. Orthotopic patient-derived xenograft mouse models demonstrated that LRRK2 inhibition with DNK72 effectively reduced tumor growth and increased survival time. We propose that LRRK2 plays a significant role in regulating the stemness of GSCs and that suppression of LRRK2 kinase activity leads to reduced GBM malignancy and proliferation. In the near future, targeting LRRK2 in patients with high LRRK2-expressing GBM could offer a superior therapeutic strategy and potentially replace current clinical treatment methods.

Published
2024
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