Angiogenic growth factor axis in autophagy regulation.
Angiogenic growth factor axis in autophagy regulation.
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DOI：
10.4161/auto.23783
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发表时间：
2013-05
期刊：
影响因子：
13.3
通讯作者：
Datta K
中科院分区：
文献类型：
--
作者：
Stanton MJ;Dutta S;Polavaram NS;Roy S;Muders MH;Datta K
了解促进治疗耐药的分子机制是重要的。在此之前，我们报道了VEGFC可以通过与其受体NRP2的相互作用促进应激状态下癌细胞的存活。在研究这种存活的分子机制时，我们进行了一项微阵列研究，确定了两个基因WDFY1和LAMP2，这两个基因被认为在自噬中起作用。我们随后的研究进一步证实了VEGFC-NRP2轴在饥饿和化疗诱导的应激过程中对癌症自噬的调节。我们目前正在确定WDFY1和LAMP2控制自噬的机制；然而，我们确实观察到在VEGFC-NRP2轴耗尽后MTOR复合物1 （MTORC1）活性增加。因此，研究WDFY1和LAMP2是否可以影响MTORC1活性并调节自噬是很有意义的。综上所述，我们的数据表明靶向VEGFC-NRP2轴联合化疗可能是晚期癌症的有效治疗方法。
Understanding the molecular mechanisms promoting therapy resistance is important. Previously, we reported that VEGFC can promote cancer cell survival during stress via interaction with its receptor NRP2. While examining the molecular mechanisms involved in this survival, we performed a microarray study in which we identified two genes, WDFY1 and LAMP2, which have been suggested to function in autophagy. Our subsequent studies further confirmed the regulation of autophagy by the VEGFC-NRP2 axis in cancer during starvation- and chemotherapy-induced stress. We are currently in the process of determining the mechanism(s) through which WDFY1 and LAMP2 control autophagy; however, we did observe an increase in MTOR complex 1 (MTORC1) activity after the depletion of the VEGFC-NRP2 axis. It would therefore be interesting to study whether WDFY1 and LAMP2 can influence MTORC1 activity and regulate autophagy. Taken together, our data suggest that targeting the VEGFC-NRP2 axis in combination with chemotherapy could be an effective treatment for advanced cancers.