| RRC ID |
49314
|
| 著者 |
Nishimura T, Tamaoki M, Komatsuzaki R, Oue N, Taniguchi H, Komatsu M, Aoyagi K, Minashi K, Chiwaki F, Shinohara H, Tachimori Y, Yasui W, Muto M, Yoshida T, Sakai Y, Sasaki H.
|
| タイトル |
SIX1 maintains tumor basal cells via transforming growth factor-β pathway and associates with poor prognosis in esophageal cancer.
|
| ジャーナル |
Cancer Sci
|
| Abstract |
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors. Although improvement in both surgical techniques and neoadjuvant chemotherapy has been achieved, the 5-year survival rate of locally advanced tumors was, at best, still 55%. Therefore, elucidation of mechanisms of the malignancy is eagerly awaited. Epithelial-mesenchymal transition (EMT) by transforming growth factor-β (TGF-β) has been reported to have critical biological roles for cancer cell stemness, whereas little is known about it in ESCC. In the current study, a transcriptional factor SIX1 was found to be aberrantly expressed in ESCCs. SIX1 cDNA transfection induced overexpression of transforming growth factors (TGFB1 and TGFB2) and its receptor (TGFBR2). Cell invasion was reduced by SIX1 knockdown and was increased in stable SIX1-transfectants. Furthermore, the SIX1-transfectants highly expressed tumor basal cell markers such as NGFR, SOX2, ALDH1A1, and PDPN. Although mock-transfectants had only a 20% PDPN-high population, SIX1-transfectants had 60-70%. In two sets of 42 and 85 ESCC patients receiving surgery alone or neoadjuvant chemoradiotherapy followed by surgery, the cases with high SIX1 mRNA and protein expression level significantly showed a poor prognosis compared with those with low levels. These SIX1 high cases also expressed the above basal cell markers, but suppressed the differentiation markers. Finally, TGF-β signaling blockade suppressed ESCC cell growth in association with the reduction of PDPN-positive tumor basal cell population. The present results suggest that SIX1 accelerates self-renewal of tumor basal cells, resulting in a poor prognosis for ESCC patients.
|
| 巻・号 |
108(2)
|
| ページ |
216-225
|
| 公開日 |
2017-2-1
|
| DOI |
10.1111/cas.13135
|
| PMID |
27987372
|
| PMC |
PMC5329162
|
| MeSH |
Carcinoma, Squamous Cell / metabolism*
Carcinoma, Squamous Cell / mortality
Carcinoma, Squamous Cell / pathology
Cell Line, Tumor
Epithelial-Mesenchymal Transition*
Esophageal Neoplasms / metabolism*
Esophageal Neoplasms / mortality
Esophageal Neoplasms / pathology
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism*
Humans
Membrane Glycoproteins / metabolism
Neoplasm Proteins / genetics
Neoplasm Proteins / metabolism*
Prognosis
Receptors, Transforming Growth Factor beta / genetics
Receptors, Transforming Growth Factor beta / metabolism*
Transfection
Transforming Growth Factor beta / genetics
Transforming Growth Factor beta / metabolism*
|
| IF |
4.966
|
| 引用数 |
13
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| 遺伝子材料 |
pcDNA3.1(+)-SIX1 (RDB15335) |
