Open AccessCritical role of estrogen receptor on anoikis and invasion of squamous cell carcinoma
Author(s) -
Ishida Hiroyuki,
Wada Koichiro,
Masuda Tomotake,
Okura Masaya,
Kohama Keiko,
Sano Yoshito,
Nakajima Atsushi,
Kogo Mikihiko,
Kamisaki Yoshinori
Publication year - 2007
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00437.x
Subject(s) - anoikis , estrogen receptor , cancer research , tamoxifen , focal adhesion , mapk/erk pathway , kinase , biology , signal transduction , microbiology and biotechnology , chemistry , programmed cell death , medicine , apoptosis , cancer , breast cancer , biochemistry
Estrogen receptor (ER) plays an important role in various physiological functions. We examined whether ERα and ERβ are expressed in squamous cell carcinoma (SCC), and whether ER is a potential target for antitumor therapy. High‐level expression of ERβ, but not ERα, was observed in tumor cells of human primary SCC tissues and various SCC cultured cell lines. Treatment with ER antagonist (tamoxifen), but not agonist (estradiol), caused apoptotic cell death of SCC cells in a concentration‐ and time‐dependent manner. Adhesion of SCC was inhibited by the treatment with tamoxifen, but not with estradiol. Tamoxifen reduced the phosphorylation of focal adhesion kinase (FAK), resulting in decreases in phosphorylation of extracellular signal‐related kinase (Erk) and mitogen‐activated protein kinase. Inhibition of FAK phosphorylation is accompanied by disorder of the cytoskeletal component actin. The cell death caused by tamoxifen is therefore the result of direct interference in cell adhesion, which is called ‘anoikis’, involving a decrease in intracellular FAK signaling. Expression of epidermal growth factor receptor was also inhibited by treatment with a high concentration of tamoxifen. Knockdown of ERβ by small interfering RNA inhibited the proliferation of SCC. In addition, tamoxifen strongly inhibited invasion of SCC. These results imply a potentially important role for ER, whose inhibition may be effective for the treatment of SCC and the prevention of invasion and metastasis. ( Cancer Sci 2007; 98: 636–643)