Wyszomierski Shannon L, Yu Dihua
Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer Cell. 2005 Dec;8(6):437-9. doi: 10.1016/j.ccr.2005.11.006.
Akt is well known to enhance malignancy and is recognized as a key target for antineoplastic therapies. However, intriguing findings reported by Yoeli-Lerner et al. in the November 23, 2005 issue of Molecular Cell, suggest a novel, antimetastasis function of Akt: activation of Akt1 inhibited invasion in some cancer cells. One possible mechanism for this surprising phenotype was that Akt activated the E3 ubiquitin ligase HDM2, causing ubiquitination and degradation of NFAT, an invasion-promoting factor. These findings clearly justify further investigations and, if validated in vivo, call for reevaluation of some Akt-targeting therapeutic strategies currently under development.
众所周知，Akt会增强恶性肿瘤的发生，并且被认为是抗肿瘤治疗的关键靶点。然而，约埃利 - 勒纳等人在2005年11月23日的《分子细胞》杂志上报道的有趣发现表明，Akt具有一种新的抗转移功能：激活Akt1可抑制某些癌细胞的侵袭。这种令人惊讶的表型的一种可能机制是，Akt激活了E3泛素连接酶HDM2，导致促进侵袭的因子NFAT发生泛素化并降解。这些发现显然为进一步研究提供了依据，如果在体内得到验证，就需要重新评估目前正在开发的一些针对Akt的治疗策略。
