Therapeutic upregulation of Class A scavenger receptor member 5 inhibits tumor growth and metastasis.
Class A scavenger receptor member 5 (SCARA5) is a new member of the Class A scavenger receptors that has been proposed recently as a novel candidate tumor suppressor gene in human hepatocellular carcinoma. In the present study, we found that SCARA5 expression was frequently downregulated in various cancer cell lines and tumor samples. In addition, upregulation of SCARA5 expression in human cancer cell line (U251) led to a significant decrease in cell proliferation, clone formation, migration, and invasion in vitro. Furthermore, systemic treatment of tumor-bearing mice with SCARA5-cationic liposome complex not only reduced the growth of subcutaneous human glioma tumors, but also markedly suppressed the spontaneous formation of lung metastases. Similar results were obtained in another experiment using mice bearing experimental A549 lung metastases. Compared with the untreated control group, mice treated with SCARA5 exhibited reductions in both spontaneous U251 and experimental A549 lung metastases rates of 77.3% and 70.2%, respectively. Western blot analysis was used to explore the molecular mechanisms involved and revealed that SCARA5 physically associated with focal adhesion kinase. Interestingly, upregulation of SCARA5 inactivated signal transducer and activator of transcription 3, as well as downstream signaling including cyclinB1, cyclinD1, AKT, survivin, matrix metalloproteinase-9 and vascular endothelial growth factor-A. Overall, the findings of the present study provide the first evidence that SCARA5 might be a promising target for the development of new antimetastatic agents for the gene therapy of cancer.
State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Nv
N
Yan
Shuang
S
Zhang
Yang
Y
Yang
Lin
L
Cheng
Can
C
Li
Lixia
L
Dai
Lei
L
Dai
Xiaomei
X
Zhang
Ping
P
Fan
Hongwei
H
Tian
Ruibo
R
Wang
Xiaolei
X
Chen
Xiaolan
X
Su
Yiming
Y
Li
Junfeng
J
Zhang
Tao
T
Du
Yuquan
Y
Wei
Hongxin
H
Deng
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000235:genetics; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D047368:Tumor Burden / Q000235:genetics; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
C569833:SCARA5 protein, human; D050796:STAT3 Transcription Factor; D051117:Scavenger Receptors, Class A; D051416:Focal Adhesion Protein-Tyrosine Kinases