Urokinase-type plasminogen activator receptor signaling is critical in nasopharyngeal carcinoma cell growth and metastasis.
Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in southern China and Southeast Asia, with the highest metastasis rate among head and neck cancers. The mechanisms underlying NPC progression remain poorly understood. Genome-wide expression profiling on 18 NPC vs. 18 noncancerous nasopharyngeal tissues together with GeneGo pathway analysis and expression verification in NPC cells and tissues revealed a potential role of urokinase-type plasminogen activator receptor (uPAR) in NPC progression, which has not been investigated in NPC. We then observed that uPAR expression is increased in poorly differentiated, highly metastatic NPC cells compared with lowly metastatic cells or differentiated NPC cells. In vitro studies demonstrated that uPAR regulates NPC cell growth, colony formation, migration, and invasion and promotes the epithelial-mesenchymal transition (EMT). Additional tumor xenograft and spontaneous metastasis experiments revealed that uPAR promotes NPC cell growth and metastasis in vivo. The JAK-STAT pathway is involved in uPAR-regulated signaling in NPC cells as determined by immunoblotting. Moreover, uPAR-mediated growth and motility is partially abolished upon treatment with the Jak1/Jak2 inhibitor INCB018424. We suppressed uPA expression in uPAR-overexpressing NPC cells and found that uPAR-mediated cellular growth and motility is not exclusively dependent on uPA. In summary, uPAR is a significant regulator of NPC progression and could serve as a promising therapeutic target.
State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center; Guangzhou, China; Department of Radiotherapy; Affiliated Hospital of Inner Mongolia Medical University; Hohhot City, Inner Mongolia Autonomous Region, China.
Ying-Na
YN
Bao
State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center; Guangzhou, China.
Xue
X
Cao
Department of Nasopharyngeal Carcinoma; Sun Yat-sen University Cancer Center; Guangzhou, China.
Dong-Hua
DH
Luo
Department of Nasopharyngeal Carcinoma; Sun Yat-sen University Cancer Center; Guangzhou, China.
Rui
R
Sun
State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center; Guangzhou, China.
Li-Xia
LX
Peng
Department of Nasopharyngeal Carcinoma; Sun Yat-sen University Cancer Center; Guangzhou, China.
Lin
L
Wang
Gencode Technologies; Saint Charles, MO USA.
Yong-Pan
YP
Yan
State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center; Guangzhou, China.
Li-Sheng
LS
Zheng
State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center; Guangzhou, China.
Ping
P
Xie
State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center; Guangzhou, China.
Yun
Y
Cao
State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center; Guangzhou, China.
Ying-Ying
YY
Liang
State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center; Guangzhou, China.
Fang-Jing
FJ
Zheng
State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center; Guangzhou, China.
Bi-Jun
BJ
Huang
Department of Nasopharyngeal Carcinoma; Sun Yat-sen University Cancer Center; Guangzhou, China.
Yan-Qun
YQ
Xiang
Department of Nasopharyngeal Carcinoma; Sun Yat-sen University Cancer Center; Guangzhou, China.
Xing
X
Lv
Department of Nasopharyngeal Carcinoma; Sun Yat-sen University Cancer Center; Guangzhou, China.
Qiu-Yan
QY
Chen
Department of Nasopharyngeal Carcinoma; Sun Yat-sen University Cancer Center; Guangzhou, China.
Ming-Yuan
MY
Chen
Department of Nasopharyngeal Carcinoma; Sun Yat-sen University Cancer Center; Guangzhou, China.
Pei-Yu
PY
Huang
Department of Nasopharyngeal Carcinoma; Sun Yat-sen University Cancer Center; Guangzhou, China.
Ling
L
Guo
Department of Nasopharyngeal Carcinoma; Sun Yat-sen University Cancer Center; Guangzhou, China.
Hai-Qiang
HQ
Mai
Department of Nasopharyngeal Carcinoma; Sun Yat-sen University Cancer Center; Guangzhou, China.
Xiang
X
Guo
State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center; Guangzhou, China.
Yi-Xin
YX
Zeng
State Key Laboratory of Oncology in South China; Sun Yat-sen University Cancer Center; Guangzhou, China; Department of Nasopharyngeal Carcinoma; Sun Yat-sen University Cancer Center; Guangzhou, China.
Chao-Nan
CN
Qian
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D002277:Carcinoma; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005260:Female; D064593:Heterografts; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology*; D009362:Neoplasm Metastasis; D009570:Nitriles; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D004791:Enzyme Inhibitors; D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; D055293:Receptors, Urokinase Plasminogen Activator; D050791:STAT Transcription Factors; C540383:ruxolitinib; D053612:Janus Kinases
JAK; STAT; genome-wide expression profiling; metastasis; nasopharyngeal carcinoma; tumor growth; uPAR