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Knockdown of CD44 inhibits the invasion and metastasis of hepatocellular carcinoma both in vitro and in vivo by reversing epithelial-mesenchymal transition.

Gao Y, Ruan B, Liu W, Wang J, Yang X, Zhang Z, Li X, Duan J, Zhang F, Ding R, Tao K, Dou K - Oncotarget (2015)

Bottom Line: First, we noticed that CD44 expression was associated with the mesenchymal phenotype in HCC cell lines, and knocking down CD44 with lentivirus-mediated shRNA in HCC cell lines resulted in the mesenchymal-epithelial-transition (MET) and the subsequent impaired migration and invasion in vitro.Moreover, in a metastatic mice model established by tail vein injection of luciferase labelled MHCC97-H cells, we confirmed that CD44 knockdown resulted in the decreased metastasis of HCC cells.Furthermore, we found that the induction of MET by CD44 inhibition might be achieved, at least in part, by repressing the ERK/Snail pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepato-Biliary and Pancreto-Splenic Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.

ABSTRACT
Mounting evidence has shown that induction of epithelial-mesenchymal transition (EMT) contributes to the the expression of CSC (cancer stem cell) markers. However, whether and how CSC markers could be involved in regulating EMT has rarely been reported. CD44, being one of the most commonly used CSC markers in hepatocellular carcinoma (HCC), has been demonstrated to act as a multidomain, transmembrane platform that serves to integrate a wide variety of extracellular signals. Therefore, we determined to seek whether CD44 is necessary for the EMT process in HCC. First, we noticed that CD44 expression was associated with the mesenchymal phenotype in HCC cell lines, and knocking down CD44 with lentivirus-mediated shRNA in HCC cell lines resulted in the mesenchymal-epithelial-transition (MET) and the subsequent impaired migration and invasion in vitro. Moreover, in a metastatic mice model established by tail vein injection of luciferase labelled MHCC97-H cells, we confirmed that CD44 knockdown resulted in the decreased metastasis of HCC cells. Furthermore, we found that the induction of MET by CD44 inhibition might be achieved, at least in part, by repressing the ERK/Snail pathway.

No MeSH data available.


Related in: MedlinePlus

CD44 knockdown inhibited the migration and invasion of MHCC97-H and SMMC-7721 cellsMigration (A) and matrigel invasion (C) assays of SMMC-7721 and MHCC97-H cells that were transfected with shRNA of CD44 or NC were evaluated. Migrated (B) and invaded (D) cells were counted under 3 randomised 200× field (* means p<0.05, ** means p<0.01, *** means p<0.001 by T test).
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Figure 3: CD44 knockdown inhibited the migration and invasion of MHCC97-H and SMMC-7721 cellsMigration (A) and matrigel invasion (C) assays of SMMC-7721 and MHCC97-H cells that were transfected with shRNA of CD44 or NC were evaluated. Migrated (B) and invaded (D) cells were counted under 3 randomised 200× field (* means p<0.05, ** means p<0.01, *** means p<0.001 by T test).

Mentions: As cell migration and invasion properties are important consequences of the EMT [25, 26], we investigated the impact of CD44 knockdown on the migration (Fig. 3A) and invasion (Fig. 3C) of SMMC-7721 and MHCC97-H cells with transwell migration and invasion assays. We found that the migration rate of SMMC-7721-KD and MHCC97-H-KD cells decreased by 41.03% and 46.31% (Fig. 3B) and that the invasion rate of SMMC-7721-KD and MHCC97-H-KD cells decreased by 36.18% and 33.62% (Fig. 3D), compared with SMMC-7721-NC and MHCC97-H-NC cells, respectively.


Knockdown of CD44 inhibits the invasion and metastasis of hepatocellular carcinoma both in vitro and in vivo by reversing epithelial-mesenchymal transition.

Gao Y, Ruan B, Liu W, Wang J, Yang X, Zhang Z, Li X, Duan J, Zhang F, Ding R, Tao K, Dou K - Oncotarget (2015)

CD44 knockdown inhibited the migration and invasion of MHCC97-H and SMMC-7721 cellsMigration (A) and matrigel invasion (C) assays of SMMC-7721 and MHCC97-H cells that were transfected with shRNA of CD44 or NC were evaluated. Migrated (B) and invaded (D) cells were counted under 3 randomised 200× field (* means p<0.05, ** means p<0.01, *** means p<0.001 by T test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480719&req=5

Figure 3: CD44 knockdown inhibited the migration and invasion of MHCC97-H and SMMC-7721 cellsMigration (A) and matrigel invasion (C) assays of SMMC-7721 and MHCC97-H cells that were transfected with shRNA of CD44 or NC were evaluated. Migrated (B) and invaded (D) cells were counted under 3 randomised 200× field (* means p<0.05, ** means p<0.01, *** means p<0.001 by T test).
Mentions: As cell migration and invasion properties are important consequences of the EMT [25, 26], we investigated the impact of CD44 knockdown on the migration (Fig. 3A) and invasion (Fig. 3C) of SMMC-7721 and MHCC97-H cells with transwell migration and invasion assays. We found that the migration rate of SMMC-7721-KD and MHCC97-H-KD cells decreased by 41.03% and 46.31% (Fig. 3B) and that the invasion rate of SMMC-7721-KD and MHCC97-H-KD cells decreased by 36.18% and 33.62% (Fig. 3D), compared with SMMC-7721-NC and MHCC97-H-NC cells, respectively.

Bottom Line: First, we noticed that CD44 expression was associated with the mesenchymal phenotype in HCC cell lines, and knocking down CD44 with lentivirus-mediated shRNA in HCC cell lines resulted in the mesenchymal-epithelial-transition (MET) and the subsequent impaired migration and invasion in vitro.Moreover, in a metastatic mice model established by tail vein injection of luciferase labelled MHCC97-H cells, we confirmed that CD44 knockdown resulted in the decreased metastasis of HCC cells.Furthermore, we found that the induction of MET by CD44 inhibition might be achieved, at least in part, by repressing the ERK/Snail pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepato-Biliary and Pancreto-Splenic Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.

ABSTRACT
Mounting evidence has shown that induction of epithelial-mesenchymal transition (EMT) contributes to the the expression of CSC (cancer stem cell) markers. However, whether and how CSC markers could be involved in regulating EMT has rarely been reported. CD44, being one of the most commonly used CSC markers in hepatocellular carcinoma (HCC), has been demonstrated to act as a multidomain, transmembrane platform that serves to integrate a wide variety of extracellular signals. Therefore, we determined to seek whether CD44 is necessary for the EMT process in HCC. First, we noticed that CD44 expression was associated with the mesenchymal phenotype in HCC cell lines, and knocking down CD44 with lentivirus-mediated shRNA in HCC cell lines resulted in the mesenchymal-epithelial-transition (MET) and the subsequent impaired migration and invasion in vitro. Moreover, in a metastatic mice model established by tail vein injection of luciferase labelled MHCC97-H cells, we confirmed that CD44 knockdown resulted in the decreased metastasis of HCC cells. Furthermore, we found that the induction of MET by CD44 inhibition might be achieved, at least in part, by repressing the ERK/Snail pathway.

No MeSH data available.


Related in: MedlinePlus