LASP1 is a HIF1α target gene critical for metastasis of pancreatic cancer.
LASP1 is an actin-binding protein associated with actin assembly dynamics in cancer cells. Here, we report that LASP1 is overexpressed in pancreatic ductal adenocarcinoma (PDAC) where it promotes invasion and metastasis. We found that LASP1 overexpression in PDAC cells was mediated by HIF1α through direct binding to a hypoxia response element in the LASP1 promoter. HIF1α stimulated LASP1 expression in PDAC cells in vitro and mouse tumor xenografts in vivo. Clinically, LASP1 overexpression in PDAC patient specimens was associated significantly with lymph node metastasis and overall survival. Overall, our results defined LASP1 as a direct target gene for HIF1α upregulation that is critical for metastatic progression of PDAC.
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China. Department of Pancreatic Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Tiansuo
T
Zhao
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China. Department of Pancreatic Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
He
H
Ren
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China. Department of Pancreatic Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Jing
J
Li
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China. Department of Pancreatic Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Jing
J
Chen
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China. Department of Pancreatic Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Huan
H
Zhang
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China. Department of Pancreatic Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Wen
W
Xin
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China. Department of Pancreatic Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Yan
Y
Sun
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China. Department of Pancreatic Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Lei
L
Sun
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China. Department of Pancreatic Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Yongwei
Y
Yang
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China. Department of Pancreatic Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Junwei
J
Sun
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China. Department of Pancreatic Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Xiuchao
X
Wang
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China. Department of Pancreatic Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Song
S
Gao
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China. Department of Pancreatic Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Chongbiao
C
Huang
School of Life Science, University of Science and Technology of China, Hefei, Anhui, China.
Huafeng
H
Zhang
Department of Tumor Biology and Comprehensive Melanoma Research Center, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
Shengyu
S
Yang
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China. Department of Pancreatic Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China. haojihui@tjmuch.com.
Jihui
J
Hao
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D064593:Heterografts; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D060588:LIM Domain Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D018398:Homeodomain Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C096353:LASP1 protein, human; D060588:LIM Domain Proteins; C490692:Lasp1 protein, mouse