Receptor for activated C kinase 1 (RACK1): a regulator for migration and invasion in oral squamous cell carcinoma cells.
OBJECTIVE
Receptor of activated protein kinase C 1 (RACK1) has been identified as an anchoring or adaptor protein in multiple intracellular signal transduction pathways. Our previous study has showed that the expression of RACK1 was paralleled with proliferation and correlated with metastasis and clinical outcome. However, the underlined mechanism has not been uncovered.


METHODS
We first selected a most effective siRNA among three siRNAs (siRNA-1, siRNA-2 and siRNA-3) targeting different regions in the RACK1 mRNA and re-evaluated the anticancer effect of RACK1 silencing on HSC-3 and Cal-27 cell lines by cell growth inhibition. And then, we investigated whether knockdown of RACK1 could inhibit cell adhesion, migration and invasion in these two cell lines. To further understand the molecular mechanism of RACK1 in these processes, the expressions of EGFR, pEGFR, HER2, MMP-2 and MMP-9 were detected by western blot.


RESULTS
We verified that the silence of RACK1 gene in two OSCC cell lines could not only inhibit cell proliferation but also decrease the invasion, migration and adhesion capability of the tumor cells. Further, western blot analysis deduced that it might be related to the decrease in protein expression of EGFR, pEGFR, HER2, MMP-2 and MMP-9.


CONCLUSIONS
Our results clearly showed the significance of RACK1-induced OSCC cell migration, invasion and adhesion, which could explain the underlined mechanism of the effect of the gene on metastasis and clinical outcome. Also, our results confirmed its role to be a prognostic indicator and a promising drug target for OSCC cell metastasis.
State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, No. 14, Sec.3, Renminnan Road, Chengdu 610041, Sichuan, China.
Jing
J
Li
Yu
Y
Guo
Xiaodong
X
Feng
Zhiyong
Z
Wang
Yun
Y
Wang
Peng
P
Deng
Dunfang
D
Zhang
Ruinan
R
Wang
Liang
L
Xie
Xiaoping
X
Xu
Yu
Y
Zhou
Ning
N
Ji
Jing
J
Hu
Min
M
Zhou
Ga
G
Liao
Ning
N
Geng
Lu
L
Jiang
Zhi
Z
Wang
Qianming
Q
Chen
D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D034622:RNA Interference; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D066246:ErbB Receptors; D019204:GTP-Binding Proteins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; C419368:RACK1 protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C522361:MMP2 protein, human