title: S100A4 protects gastric cancer cells from anoikis through regulation of αv and α5 integrin.
abstract: Detachment from the extracellular matrix induces a form of programmed cell death termed anoikis. Resistance to anoikis permits cancer cells to survive in systemic circulation and facilitates their metastasis to distant organs. It is well known that S100A4 is overexpressed in many tumors and involved in tumor metastasis, but the mechanisms of the metastasis-promoting function of S100A4 are not fully understood. We hypothesized that S100A4 might play a role in anoikis of gastric cancer cells and further affects their metastasis. To test this hypothesis, we changed the expression of S100A4 by means of RNA interference or experimental overexpression and investigated the effect on anoikis. We found that knockdown of S100A4 by RNA interference led to significantly increased anoikis, whereas overexpression of S100A4 resulted in inhibition of anoikis. Furthermore, we provide evidence that inhibition of S100A4 resulted in the downregulation of α5 and αv integrin expression. These findings suggest that S100A4 protects gastric cancer cells from anoikis by regulation of αv and α5 integrin expression, which sheds a novel light for the role of S100A4 in cancer metastasis.
authors.affiliation: Department of Medical Genetics, China Medical University, Shenyang, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
authors.forename: Danqi
authors.initials: D
authors.lastname: Chen
authors.forename: Hao
authors.initials: H
authors.lastname: Fu
authors.forename: Shanshan
authors.initials: S
authors.lastname: Liu
authors.forename: Kailai
authors.initials: K
authors.lastname: Sun
authors.forename: Xiuju
authors.initials: X
authors.lastname: Sun
mesh_terms: D023102:Anoikis / Q000502:physiology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D039482:Integrin alpha5 / Q000096:biosynthesis* / Q000235:genetics; D039564:Integrin alphaV / Q000096:biosynthesis* / Q000235:genetics; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D039482:Integrin alpha5; D039564:Integrin alphaV; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human