In:
PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 1 ( 2022-1-10), p. e0262485-
Abstract:
Selective estrogen receptor modulator (SERM) interacts with estrogen receptors and acts as both an agonist or an antagonist, depending on the target tissue. SERM is widely used as a safer hormone replacement therapeutic medicine for postmenopausal osteoporosis. Regarding hepatocellular carcinoma (HCC), accumulating evidence indicates gender differences in the development, and that men are at higher morbidity risk than premenopausal women, suggesting that estrogen protects against HCC. However, it remains unclear whether SERM affects the HCC progression. Previously, we have shown that transforming growth factor (TGF)-α promotes the migration of HCC cells via p38 mitogen-activated protein kinases (MAPK), c- Jun N-terminal kinase and AKT. In the present study, we investigated whether SERM such as tamoxifen, raloxifene and bazedoxifene, affects the HCC cell migration using human HCC-derived HuH7 cells. Raloxifene and bazedoxifene but not tamoxifen, significantly suppressed the TGF-α-induced HuH7 cell migration. ERB041 and DPN, estrogen receptor (ER) β agonists, inhibited the TGF-α-induced cell migration whereas PPT, an ERα agonist, did not show the suppressive effect on the cell migration. ERB041 attenuated the TGF-α-induced phosphorylation of AKT without affecting the phosphorylation of p38 MAPK and c-Jun N-terminal kinase. Raloxifene and bazedoxifene also inhibited the phosphorylation of AKT by TGF-α. Furthermore, PHTPP, an ERβ antagonist, significantly reversed the suppression by both raloxifene and bazedoxifene of the TGF-α-induced cell migration. Taken together, our results strongly indicate that raloxifene and bazedoxifene, SERMs, suppress the TGF-α-induced migration of HCC cells through ERβ-mediated inhibition of the AKT signaling pathway.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0262485
DOI:
10.1371/journal.pone.0262485.g001
DOI:
10.1371/journal.pone.0262485.g002
DOI:
10.1371/journal.pone.0262485.g003
DOI:
10.1371/journal.pone.0262485.g004
DOI:
10.1371/journal.pone.0262485.g005
DOI:
10.1371/journal.pone.0262485.g006
DOI:
10.1371/journal.pone.0262485.g007
DOI:
10.1371/journal.pone.0262485.g008
DOI:
10.1371/journal.pone.0262485.g009
DOI:
10.1371/journal.pone.0262485.g010
DOI:
10.1371/journal.pone.0262485.g011
DOI:
10.1371/journal.pone.0262485.g012
DOI:
10.1371/journal.pone.0262485.s001
DOI:
10.1371/journal.pone.0262485.s002
DOI:
10.1371/journal.pone.0262485.s003
DOI:
10.1371/journal.pone.0262485.s004
DOI:
10.1371/journal.pone.0262485.s005
DOI:
10.1371/journal.pone.0262485.s006
DOI:
10.1371/journal.pone.0262485.s007
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2267670-3
Permalink