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Signal transducers and activators of transcription 3‐induced metastatic potential in gastric cancer cells is enhanced by glycogen synthase kinase‐3β
Author(s) -
Yoon Jiyeon,
Ko Young San,
Cho Sung Jin,
Park Jinju,
Choi Young Sun,
Choi Yiseul,
Pyo JungSoo,
Ye SangKyu,
Youn HongDuk,
Lee JaeSeon,
Chang Mee Soo,
Kim Min A,
Lee Byung Lan
Publication year - 2015
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/apm.12370
Subject(s) - stat3 , gsk 3 , cancer research , gsk3b , cancer , cancer cell , vimentin , metastasis , biology , chemistry , medicine , immunohistochemistry , kinase , signal transduction , pathology , microbiology and biotechnology
The transcription factor signal transducers and activators of transcription 3 ( STAT 3) can promote cancer metastasis, but its underlying regulatory mechanisms in gastric cancer cell invasiveness still remain obscure. We investigated the relationship between STAT 3 and glycogen synthase kinase‐3β ( GSK ‐3β) and its significance in metastatic potential in gastric cancer cells. Immunohistochemical tissue array analysis of 267 human gastric carcinoma specimens showed that the expressions of active forms of STAT 3 ( pSTAT 3) and GSK ‐3β ( pGSK ‐3β) were found in 68 (25%) and 124 (46%) of 267 gastric cancer cases, respectively, showing a positive correlation (p < 0.001). Cell culture experiments using gastric cancer cell lines SNU ‐638 and SNU ‐668 revealed that STAT 3 suppression did not affect pGSK ‐3β expression, whereas GSK ‐3β inhibition reduced pSTAT 3 expression. With respect to metastatic potential in gastric cancer cells, both STAT 3 suppression and GSK ‐3β inhibition decreased cell migration, invasion, and mesenchymal marker (Snail, Vimentin, and MMP 9) expression. Moreover, the inhibitory effects of STAT 3 and GSK ‐3β on cell migration were synergistic. These results demonstrated that STAT 3 and GSK ‐3β are positively associated and synergistically contribute to metastatic potential in gastric cancer cells. Thus, dual use of STAT 3 and GSK ‐3β inhibitors may enhance the efficacy of the anti‐metastatic treatment of gastric cancer.

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