Abstract
Patients with esophageal squamous cell carcinomas (ESCCs) have poor survival and high recurrence rate, but lack a prognostic biomarker. Disabled-2 (DAB2) is a crucial tumor suppressor, but its roles in ESCCs are uncertain. We investigated whether low DAB2 expression in ESCCs could lead into tumor progression and poor prognosis. Our results found patients with low-DAB2 expression ESCCs had significantly larger tumor size, deeper tumor invasion depth, lymph node metastasis, worse survival, and higher recurrence rate (P<0.05). The Cox-regression model revealed low-DAB2 expression was an independent factor of poor survival (P<0.05), and also of tumor recurrence with the predictive performance superior to clinical TNM stage (P<0.05). Low-DAB2 cancer cells, validated by DAB2 knockdown or overexpression, had higher phosphorylated ERK and migration abilities, which could be suppressed by ERK inhibitor treatment. TGF-β-induced epithelial-to-mesenchymal transition (EMT) only existed in the high-DAB2 cells, and related to worse prognosis of high-DAB2 ESCCs (P<0.05). In conclusion, DAB2 can suppress the ERK signaling, but correlate to have TGF-β-induced EMT in ESCCs. DAB2 expression could be a biomarker to identify patients with worse survival and high recurrence. Our data suggest DAB2 expression can stratify patients in need of aggressive surveillance and with possible benefit from anti-ERK or anti-TGF-β therapies.
| Original language | English |
|---|---|
| Pages (from-to) | 71169-71181 |
| Number of pages | 13 |
| Journal | Oncotarget |
| Volume | 7 |
| Issue number | 44 |
| DOIs | |
| Publication status | Published - Jan 1 2016 |
| Externally published | Yes |
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Keywords
- Disabled-2
- Esophageal cancer
- Recurrence
- Survival
ASJC Scopus subject areas
- Oncology
Cite this
Low disabled-2 expression promotes tumor progression and determines poor survival and high recurrence of esophageal squamous cell carcinoma. / Wang, Wen Lun; Chang, Wei Lun; Yang, Hsiao Bai; Wang, Yu Chi; Chang, I. Wei; Lee, Ching Tai; Chang, Chi Yang; Lin, Jaw Town; Sheu, Bor Shyang.
In: Oncotarget, Vol. 7, No. 44, 01.01.2016, p. 71169-71181.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Low disabled-2 expression promotes tumor progression and determines poor survival and high recurrence of esophageal squamous cell carcinoma
AU - Wang, Wen Lun
AU - Chang, Wei Lun
AU - Yang, Hsiao Bai
AU - Wang, Yu Chi
AU - Chang, I. Wei
AU - Lee, Ching Tai
AU - Chang, Chi Yang
AU - Lin, Jaw Town
AU - Sheu, Bor Shyang
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Patients with esophageal squamous cell carcinomas (ESCCs) have poor survival and high recurrence rate, but lack a prognostic biomarker. Disabled-2 (DAB2) is a crucial tumor suppressor, but its roles in ESCCs are uncertain. We investigated whether low DAB2 expression in ESCCs could lead into tumor progression and poor prognosis. Our results found patients with low-DAB2 expression ESCCs had significantly larger tumor size, deeper tumor invasion depth, lymph node metastasis, worse survival, and higher recurrence rate (P<0.05). The Cox-regression model revealed low-DAB2 expression was an independent factor of poor survival (P<0.05), and also of tumor recurrence with the predictive performance superior to clinical TNM stage (P<0.05). Low-DAB2 cancer cells, validated by DAB2 knockdown or overexpression, had higher phosphorylated ERK and migration abilities, which could be suppressed by ERK inhibitor treatment. TGF-β-induced epithelial-to-mesenchymal transition (EMT) only existed in the high-DAB2 cells, and related to worse prognosis of high-DAB2 ESCCs (P<0.05). In conclusion, DAB2 can suppress the ERK signaling, but correlate to have TGF-β-induced EMT in ESCCs. DAB2 expression could be a biomarker to identify patients with worse survival and high recurrence. Our data suggest DAB2 expression can stratify patients in need of aggressive surveillance and with possible benefit from anti-ERK or anti-TGF-β therapies.
AB - Patients with esophageal squamous cell carcinomas (ESCCs) have poor survival and high recurrence rate, but lack a prognostic biomarker. Disabled-2 (DAB2) is a crucial tumor suppressor, but its roles in ESCCs are uncertain. We investigated whether low DAB2 expression in ESCCs could lead into tumor progression and poor prognosis. Our results found patients with low-DAB2 expression ESCCs had significantly larger tumor size, deeper tumor invasion depth, lymph node metastasis, worse survival, and higher recurrence rate (P<0.05). The Cox-regression model revealed low-DAB2 expression was an independent factor of poor survival (P<0.05), and also of tumor recurrence with the predictive performance superior to clinical TNM stage (P<0.05). Low-DAB2 cancer cells, validated by DAB2 knockdown or overexpression, had higher phosphorylated ERK and migration abilities, which could be suppressed by ERK inhibitor treatment. TGF-β-induced epithelial-to-mesenchymal transition (EMT) only existed in the high-DAB2 cells, and related to worse prognosis of high-DAB2 ESCCs (P<0.05). In conclusion, DAB2 can suppress the ERK signaling, but correlate to have TGF-β-induced EMT in ESCCs. DAB2 expression could be a biomarker to identify patients with worse survival and high recurrence. Our data suggest DAB2 expression can stratify patients in need of aggressive surveillance and with possible benefit from anti-ERK or anti-TGF-β therapies.
KW - Disabled-2
KW - Esophageal cancer
KW - Recurrence
KW - Survival
UR - http://www.scopus.com/inward/record.url?scp=84995428222&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84995428222&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.8460
DO - 10.18632/oncotarget.8460
M3 - Article
C2 - 27036032
AN - SCOPUS:84995428222
VL - 7
SP - 71169
EP - 71181
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 44
ER -