BBRC：km23-1可使延缓癌细胞扩散

immunostaining analyses were performed as described in Section 2, and representative photos are shown (400×).

　　宾夕法尼亚州立大学医学院研究人员近期发现，靶向作用km23-1蛋白可使癌细胞扩散的速度放缓。

　　Km23-1是一种动力蛋白，在细胞内起运输物质的作用，同时它还会参与细胞的移动或迁移。迁移对于癌症扩散是必不可少的，因此，对细胞迁移的深入了解对于研发更有效的癌症疗法具有重要意义。

　　该医学院生物化学与分子生物学教授Kathleen Mulder博士希望找到在细胞移动过程中与km23-1蛋白相互联合和协作的伴随蛋白，这一移动过程还包括一些可控制蛋白活动和RhoA因子的因素。Mulder博士称：“癌细胞迁移是肿瘤扩散过程的重要组成部分。这一过程的改变会使处于局部的无侵害性受限肿瘤细胞转变为迁移性和扩散性肿瘤细胞。”

　　细胞利用蛋白活动得以在人体内移动，而蛋白是细胞的结构框架，被称为细胞骨架。蛋白活动可在细胞的最前缘形成螺纹状的纤维线，从而在细胞膜上形成前突，推动细胞前进。已知的几种蛋白可调节细胞骨架的重组，而且在几类肿瘤中更具活性。

　　Km23-1蛋白过度表达会增加纤维线的形成，而一旦这种蛋白出现削弱，细胞因子RhoA的活动也会随之减弱。众所周知，RhoA因子是一种重要的开关，可激活细胞迁移过程。Mulder博士介绍称：“Km23-1蛋白减少会导致RhoA活动减弱，明白这点之后我们推断，RhoA等开关的调控离不开km23-1蛋白，而且这种蛋白在细胞移动过程中还发挥了相关作用。”

　　为了在实验室对这一发现进行验证，研究人员采取措施使人体结肠癌细胞样本中的km23-1蛋白出现减少。试验表明，当km23-1减少后，癌细胞的迁移也随之减少。虽然人们还需做更多的研究来进一步证实这一发现，但km23-1蛋白有望成为抗肿瘤转移药物和防扩散疗法的潜在作用目标，

　　Mulder博士最后说：“抑制住km23-1就能限制肿瘤细胞扩散至身体其他部位的活动。”

Role of km23-1 in RhoA/actin-based cell migration

Abstract

km23-1 was originally identified as a TGFß receptor-interacting protein that plays an important role in TGFß signaling. Moreover, km23-1 is actually part of an ancient superfamily of NTPase-regulatory proteins, widely represented in archaea and bacteria. To further elucidate the function of km23-1, we identified novel protein interacting partners for km23-1 by using tandem affinity purification (TAP) and tandem mass spectrometry (MS). Here we show that km23-1 interacted with a class of proteins involved in actin-based cell motility and modulation of the actin cytoskeleton. We further showed that km23-1 modulates the formation of a highly organized stress fiber network. More significantly, we demonstrated that knockdown (KD) of km23-1 decreased RhoA activation in Mv1Lu epithelial cells. Finally, our results demonstrated for the first time that depletion of km23-1 inhibited cell migration of human colon carcinoma cells (HCCCs) in wound-healing assays. Overall, our findings demonstrate that km23-1 regulates RhoA and motility-associated actin modulating proteins, suggesting that km23-1 may represent a novel target for anti-metastatic therapy.