Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. Cancer metastasis is a major obstacle in clinical cancer therapy. The mechanisms underlying the metastasis of HCC remain unclear. Glucose-regulated protein 94 (GRP94) is a key protein involved in mediating cancer progression, and it is highly expressed in HCC specimens. However, the role of GRP94 in cancer metastasis is unclear. A specific short hairpin RNA (shRNA) was employed to knock down GRP94 gene expression in HCC cell lines. Wound-healing migration, transwell migration, and invasion assays were performed to determine the migration and invasive ability of HCC cells. We demonstrated that silencing GRP94 inhibited HCC cell wound healing, migration, and invasion. Furthermore, our findings indicated that GRP94 knockdown might attenuate HCC cell metastasis by inhibiting CCT8/c-Jun/EMT signaling. Our study indicated that silencing GRP94 significantly reduced the migration and invasion abilities of HCC cells. Moreover, depleting GRP94 inhibited cell migration and invasion by downregulating CCT8/c-Jun signaling. Thus, our data suggest that the GRP94/CCT8/c-Jun/EMT signaling cascade might be a new therapeutic target for HCC.
| Original language | English |
|---|---|
| Pages (from-to) | 8219-8227 |
| Number of pages | 9 |
| Journal | Tumor Biology |
| Volume | 37 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 1 2016 |
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Keywords
- CCT8
- GRP94
- HCC
- Metastasis
ASJC Scopus subject areas
- Cancer Research
Cite this
Glucose-regulated protein 94 mediates metastasis by CCT8 and the JNK pathway in hepatocellular carcinoma. / Wei, Po-Li; Huang, Chien Yu; Tai, Cheng-Jeng; Batzorig, Uyanga; Cheng, Wan Li; Hunag, Ming Te; Chang, Yu-Jia.
In: Tumor Biology, Vol. 37, No. 6, 01.06.2016, p. 8219-8227.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Glucose-regulated protein 94 mediates metastasis by CCT8 and the JNK pathway in hepatocellular carcinoma
AU - Wei, Po-Li
AU - Huang, Chien Yu
AU - Tai, Cheng-Jeng
AU - Batzorig, Uyanga
AU - Cheng, Wan Li
AU - Hunag, Ming Te
AU - Chang, Yu-Jia
PY - 2016/6/1
Y1 - 2016/6/1
N2 - Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. Cancer metastasis is a major obstacle in clinical cancer therapy. The mechanisms underlying the metastasis of HCC remain unclear. Glucose-regulated protein 94 (GRP94) is a key protein involved in mediating cancer progression, and it is highly expressed in HCC specimens. However, the role of GRP94 in cancer metastasis is unclear. A specific short hairpin RNA (shRNA) was employed to knock down GRP94 gene expression in HCC cell lines. Wound-healing migration, transwell migration, and invasion assays were performed to determine the migration and invasive ability of HCC cells. We demonstrated that silencing GRP94 inhibited HCC cell wound healing, migration, and invasion. Furthermore, our findings indicated that GRP94 knockdown might attenuate HCC cell metastasis by inhibiting CCT8/c-Jun/EMT signaling. Our study indicated that silencing GRP94 significantly reduced the migration and invasion abilities of HCC cells. Moreover, depleting GRP94 inhibited cell migration and invasion by downregulating CCT8/c-Jun signaling. Thus, our data suggest that the GRP94/CCT8/c-Jun/EMT signaling cascade might be a new therapeutic target for HCC.
AB - Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. Cancer metastasis is a major obstacle in clinical cancer therapy. The mechanisms underlying the metastasis of HCC remain unclear. Glucose-regulated protein 94 (GRP94) is a key protein involved in mediating cancer progression, and it is highly expressed in HCC specimens. However, the role of GRP94 in cancer metastasis is unclear. A specific short hairpin RNA (shRNA) was employed to knock down GRP94 gene expression in HCC cell lines. Wound-healing migration, transwell migration, and invasion assays were performed to determine the migration and invasive ability of HCC cells. We demonstrated that silencing GRP94 inhibited HCC cell wound healing, migration, and invasion. Furthermore, our findings indicated that GRP94 knockdown might attenuate HCC cell metastasis by inhibiting CCT8/c-Jun/EMT signaling. Our study indicated that silencing GRP94 significantly reduced the migration and invasion abilities of HCC cells. Moreover, depleting GRP94 inhibited cell migration and invasion by downregulating CCT8/c-Jun signaling. Thus, our data suggest that the GRP94/CCT8/c-Jun/EMT signaling cascade might be a new therapeutic target for HCC.
KW - CCT8
KW - GRP94
KW - HCC
KW - Metastasis
UR - http://www.scopus.com/inward/record.url?scp=84952663154&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84952663154&partnerID=8YFLogxK
U2 - 10.1007/s13277-015-4669-3
DO - 10.1007/s13277-015-4669-3
M3 - Article
C2 - 26718209
AN - SCOPUS:84952663154
VL - 37
SP - 8219
EP - 8227
JO - Tumor Biology
JF - Tumor Biology
SN - 1010-4283
IS - 6
ER -