Oncogenic properties of human dynactin-associated protein (dynAP)

2014 Fiscal Year Final Research Report

• Project/Area Number: 24300343
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Clinical oncology
• Research Institution: Nagahama Institute of Bio-Science and Technology
• Principal Investigator: MIZUKAMI Tamio 長浜バイオ大学, バイオサイエンス学部, 教授 (80367896)
• Co-Investigator(Kenkyū-buntansha): TAKAHASHI Rei 同志社女子大学, 薬学部, 教授 (60144565)
• Co-Investigator(Renkei-kenkyūsha): NAGAI Nobuo 長浜バイオ大学, バイオサイエンス学部, 教授 (90260281) ; NAKAMURA Toshinobu 長浜バイオ大学, バイオサイエンス学部, 准教授 (80403202) ; HASEGAWA Makoto 長浜バイオ大学, バイオサイエンス学部, 教授 (10367899) ; TSURUYAMA Tatsuaki 京都大学, 医学研究科, 准教授 (00303842) ; SASAKI Ryuzo 長浜バイオ大学, バイオサイエンス学部, 客員教授 (60077378)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 分子標的治療

Outline of Final Research Achievements

Human dynactin-associated protein (dynAP) is a transmembrane protein that promotes AktSer473 phosphorylation. In contrast to control NIH3T3 cells expressing LacZ, NIH3T3dynAP cells vigorously formed colonies on soft agar, and spheroids in anchorage-deficient three-dimensional culture. NIH3T3dynAP cells injected into nude mice produced tumors with abundant blood vessels and weak cell–cell contacts. Expression of dynAP elevated the level of rictor (an essential subunit of mTORC2). Knockdown of rictor in NIH3T3dynAP cells reduced AktSer473 phosphorylation and formation of colony in soft agar and spheroid, indicating that dynAP-induced activation of the mTORC2/AktSer473 pathway for cell survival contributes to cell transformation. E-cadherin and its mRNA were markedly reduced upon expression of dynAP, giving rise to cells with higher motility, which may be responsible for the weak cell-cell adhesion in tumors. Thus, dynAP could be a new oncoprotein and a target for cancer therapy.

Free Research Field

腫瘍治療学