Galectin-3 increases gastric cancer cell motility by up-regulating fascin-1 expression.
OBJECTIVE
Galectin-3 is a beta-galactoside-binding protein that increases gastric cancer cell motility in response to integrin signaling and is highly expressed in gastric tumor cells. Galectin-3 induces cytoskeletal remodeling to increase cell motility, but the mechanisms of this process are not understood. We investigated the effects of galectin-3 on fascin-1, an actin-bundling protein.


METHODS
We collected malignant and normal tissues from gastric cancer patients and examined the expression levels of galectin-3 and fascin-1. We silenced galectin-3 expression in human gastric cancer cell lines using small interfering RNA and lenti-viral constructs and determined the effects on fascin-1 expression, cell motility, and invasion.


RESULTS
Malignant gastric tissues expressed high levels of galectin-3 and fascin-1, compared with normal gastric tissues. Silencing of galectin-3 resulted in altered cancer cell morphology, reduced fascin-1 expression, decreased cell motility, and reduced malignant cell invasion. Galectin-3 overexpression reversed these effects. Silencing of fascin-1 also reduced cell motility and caused changes in cell shape, as did silencing of galectin-3. Furthermore, galectin-3 silencing inhibited the interaction between glycogen synthase kinase (GSK)-3beta, beta-catenin, and T-cell factor (TCF) 4, and the binding of beta-catenin/TCF-4 to the fascin-1 promoter. Nuclear localization of GSK-3beta and beta-catenin were not detected when galectin-3 was silenced. Overexpression of mutated galectin-3 (with mutations in the GSK-3beta binding and phosphorylation motifs) did not increase fascin-1 levels, in contrast to overexpression of wild-type galectin-3.


CONCLUSIONS
Galectin-3 increases cell motility by up-regulating fascin-1 expression. Galectin-3 might be a potential therapeutic target for the prevention and treatment of gastric cancer progression.
Kim
Seok-Jun
SJ
Gastric Cancer Branch, Division of Translational and Clinical Research I, National Cancer Center Research Institute and Hospital, Jungbalsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, Republic of Korea.
Choi
Il-Ju
IJ
Cheong
Teak-Chin
TC
Lee
Sang-Jin
SJ
Lotan
Reuben
R
Park
Seok Hee
SH
Chun
Kyung-Hee
KH
D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D048430:Cell Shape; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D051820:TCF Transcription Factors / Q000378:metabolism; D058118:Transcription Factor 7-Like 2 Protein; D014162:Transfection; D015854:Up-Regulation; D051176:beta Catenin / Q000378:metabolism
C495270:CTNNB1 protein, human; D002352:Carrier Proteins; C502658:FSCN1 protein, human; D037502:Galectin 3; D008840:Microfilament Proteins; D012333:RNA, Messenger; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3