Galectin-1 induces invasion and the epithelial-mesenchymal transition in human gastric cancer cells via non-canonical activation of the hedgehog signaling pathway.
Galectin-1 (Gal-1) has been reported to be an independent prognostic indicator of poor survival in gastric cancer and overexpression of Gal-1 enhances the invasiveness of gastric cancer cells. However, the downstream mechanisms by which Gal-1 promotes invasion remains unclear. Moreover, the function of Gal-1 in the epithelial-mesenchymal transition (EMT) in gastric cancer has not yet been elucidated. In this study, we observed Gal-1 expression was upregulated and positively associated with metastasis and EMT markers in 162 human gastric cancer tissue specimens. In vitro studies showed Gal-1 induced invasion, the EMT phenotype and activated the non-canonical hedgehog (Hh) pathway in gastric cancer cell lines. Furthermore, our data revealed that Gal-1 modulated the non-canonical Hh pathway by increasing the transcription of glioma-associated oncogene-1 (Gli-1) via a Smoothened (SMO)-independent manner, and that upregulation of Gal-1 was strongly associated with gastric cancer metastasis. We conclude that Gal-1 promotes invasion and the EMT in gastric cancer cells via activation of the non-canonical Hh pathway, suggesting Gal-1 could represent a promising therapeutic target for the prevention and treatment of gastric cancer metastasis.
Department of Gastrointestinal Surgery, Clinical Medical College of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou 225001, China.
Yang
Y
Chong
Department of Gastrointestinal Surgery, Clinical Medical College of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou 225001, China.
Dong
D
Tang
Department of Gastrointestinal Surgery, Clinical Medical College of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou 225001, China.
Jun
J
Gao
Department of Gastrointestinal Surgery, Clinical Medical College of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou 225001, China.
Xuetong
X
Jiang
Department of Gastrointestinal Surgery, Clinical Medical College of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou 225001, China.
Chuanqi
C
Xu
Department of Gastrointestinal Surgery, Clinical Medical College of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou 225001, China.
Qingquan
Q
Xiong
Department of Gastrointestinal Surgery, Clinical Medical College of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou 225001, China.
Yuqin
Y
Huang
Department of Gastrointestinal Surgery, Clinical Medical College of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou 225001, China.
Jie
J
Wang
Department of Gastrointestinal Surgery, Clinical Medical College of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou 225001, China.
Huaicheng
H
Zhou
Department of Gastrointestinal Surgery, Clinical Medical College of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou 225001, China.
Youquan
Y
Shi
Department of Gastrointestinal Surgery, Clinical Medical College of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou 225001, China.
Daorong
D
Wang
D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D037483:Galectin 1 / Q000235:genetics / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010641:Phenotype; D034622:RNA Interference; D015398:Signal Transduction; D000072086:Smoothened Receptor / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014162:Transfection; D015854:Up-Regulation; D000071676:Zinc Finger Protein GLI1 / Q000235:genetics / Q000378:metabolism
C400551:GLI1 protein, human; D037483:Galectin 1; D053823:Hedgehog Proteins; C445499:LGALS1 protein, human; C491023:SMO protein, human; D000072086:Smoothened Receptor; D000071676:Zinc Finger Protein GLI1
Gli-1; epithelial-mesenchymal transition; galectin-1; gastric cancer; hedgehog signaling