CD44 acts through RhoA to regulate YAP signaling
Authors: Yuchen Zhang
Feng Bi
Qi Chen
Qiulin Tang
Weibing Leng
Qingjuan Chen
Hongwei Xia
Dandan Yuan
Liang Chen
Xiaojun Ge
Journal: Cellular Signalling (2014)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CD44; Hippo; RhoA; YAP.
Affiliations: Department of Medical Oncology and Laboratory of Molecular Targeted Cancer Therapy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, China., Department of Medical Oncology and Laboratory of Molecular Targeted Cancer Therapy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, China. Electronic address: .

Abstract:  The Hippo pathway plays an important role in both physical and pathogenesis processes. As crucial downstream effectors of Hippo pathway, YAP is inhibited by Lats1/2 through phosphorylation. However, upstream signals that regulate the Hippo pathway have been still poorly understood. Here, we found that knockdown of CD44 reduced YAP expression and nuclear localization, but nearly had no effect on its upstream effectors, Mst1 and Lats1. Downregulated CD44 expression also significantly decreased the expression of YAP downstream effectors CTGF, Cyr61 and EDN1 at mRNA level. Our next study showed that knockdown of CD44 inhibited RhoA expression, which was consistent with RhoA knockdown mediated YAP downregulation. Furthermore, we demonstrated that over expression of the constitutively active RhoA (RhoA-V14) could block the YAP expression decrease mediated by CD44 knockdown. Moreover, downregulation of CD44 significantly promoted cell apoptosis and inhibited cell proliferation, cell cycle progression and migration, which were consistent with the effects of RNAi-mediated YAP knockdown in both A549 and HepG2 cells. Overall, data are presented showing that CD44 could act through RhoA signaling to regulate YAP expression and this study also provide new insights into the regulatory mechanisms of the Hippo-YAP pathway. 

Retracted: No

PubPeer comments:
 Figure 1 * Red boxes: The LATS1 panels in A (A549 cells) and B (HepG2 cells) look more similar than expected. ![file] , 
 Figure 2B * Green boxes: Two lanes in the Nuc CD44 panel look remarkably similar ![file] , 
 #1 Dear Dr. Elisabeth M Bik, Thanks for your your comments for this paper. Below is my point to point response for your comments: Figure 1 Red boxes: The LATS1 panels in A (A549 cells) and B (HepG2 cells) look more similar than expected. Response: Though the bands of LATS1 in Fig 1A look similar to that in Fig 1B, they are not the same bands. Look carefully, you will find that the bands in Fig1A are much wider and shorter than that in Fig 1B. In addition, the position of the right bands in Fig1A is higher than that in Fig 1B. Lastly, after adjusting the brightness, contrast and sharpening of the total Fig 1, there are several significantly different fields between Fig1A and Fig1B, which were labeled with red circle. Therefore, the bands in Fig1A and Fig1B look similar, but they are not the same bands.![file] , 
 #2 Figure 2B Green boxes: Two lanes in the Nuc CD44 panel look remarkably similar Response: Though the two lanes in the Nuc CD44 panel look similar in Fig 2B, they are not the same bands. Firstly, the left band is much shorter and wider than the right band. Secondly, after adjusting the brightness, contrast and sharpening of the Fig2, the boundary of the whole band is neat and smooth, the band is no possible to be spliced by PS (see the red box). In addition, the background of the two bands is also different. And there are also several different fields between the two bands, which were labeled with red circle. Therefore, they are not the same bands. And the conclusions of this paper are also repeatable. ![file] , 
 Dear Dr. Zhang, I am afraid your statement that these are not the same bands is not very convincing. In particular for Figure 2B, the two bands appear to differ in width, but otherwise are remarkably similar. I could be convinced, however, if you were able to show me the uncropped, high-resolution original blots. Would you still have these available? , 
 #1 and #3 See comparison of the 2 when superimposing one over another. I agree with #1 Dr. Bik that these 2 are remarkably similar. ![file] , 
 #5 Dear Dr. Bik, I am so sorry that I can not find the original blots because it is so long time. Anyway, itu2019s all my fault not to keep the original data properly. However, there is a real difference in detail between the two bands. Thanks again for your attention and understanding to our work. , 
 #6 Dear Dr. Buddha, Thanks for your attention and comments to our work. As you mentioned, the two panels look similar, but there are difference in details between the two panels as above response. They are not the same bands. Thanks again for your attention. ,