RRC ID 67454
Author Yokobori T, Bao P, Fukuchi M, Altan B, Ozawa D, Rokudai S, Bai T, Kumakura Y, Honjo H, Hara K, Sakai M, Sohda M, Miyazaki T, Ide M, Nishiyama M, Oyama T, Kuwano H.
Title Nuclear PROX1 is Associated with Hypoxia-Inducible Factor 1α Expression and Cancer Progression in Esophageal Squamous Cell Carcinoma.
Journal Ann Surg Oncol
Abstract BACKGROUND:Transcription factor prospero homeobox 1 (PROX1) has been identified as a master regulator of lymphangiogenesis associated with metastasis. Although PROX1 expression has been investigated in several cancers, its clinical significance remains controversial and needs further validation. In this study, we investigated the clinical and functional significance of PROX1 and PROX1 regulator hypoxia-inducible factor 1α (HIF1α) in esophageal squamous cell carcinoma (ESCC).
METHODS:A total of 117 samples from ESCC patients were analyzed for PROX1, HIF1α, and E-cadherin expression by immunohistochemistry; correlation with clinicopathological characteristics was determined. PROX1 function was evaluated in PROX1 small interfering RNA (siRNA)-transfected human ESCC cells in vitro by assessing cell proliferation and migration.
RESULTS:PROX1 expression was higher in ESCC than in normal tissues. Patients with higher PROX1 expression (n = 26) had increased nuclear accumulation of HIF1α (p = 0.004) and more advanced metastasis, both lymph node (N factor; p = 0.09) and hematogenous (M factor; p = 0.04), than those with lower PROX1 expression (n = 91). In addition, high PROX1 and HIF1α expression correlated with low levels of E-cadherin, an epithelial cell marker. Analysis of overall and cancer-specific survival indicated that elevated PROX1 expression was significantly correlated with poor prognosis (p = 0.0064). PROX1 downregulation in ESCC cells inhibited cellular proliferation and migration (p < 0.05). Hypoxia restored PROX1 levels that were reduced by PROX1-specific siRNA.
CONCLUSION:Our data suggest that high expression of PROX1 in ESCC could be used as an indicator of poor prognosis, and that PROX1 is a promising candidate molecular target for ESCC treatment.
Volume 22 Suppl 3
Pages S1566-73
Published 2015-12-1
DOI 10.1245/s10434-015-4831-6
PII 10.1245/s10434-015-4831-6
PMID 26310281
MeSH Adult Aged Aged, 80 and over Biomarkers, Tumor / metabolism* Blotting, Western Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / pathology* Carcinoma, Squamous Cell / surgery Cell Movement Cell Nucleus / metabolism* Cell Proliferation Esophageal Neoplasms / metabolism Esophageal Neoplasms / pathology* Esophageal Neoplasms / surgery Female Follow-Up Studies Gene Expression Regulation, Neoplastic Homeodomain Proteins / antagonists & inhibitors Homeodomain Proteins / genetics Homeodomain Proteins / metabolism* Humans Hypoxia-Inducible Factor 1, alpha Subunit / metabolism* Immunoenzyme Techniques Male Middle Aged Neoplasm Invasiveness Neoplasm Staging Prognosis RNA, Small Interfering / genetics Survival Rate Tumor Cells, Cultured Tumor Suppressor Proteins / antagonists & inhibitors Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism*
IF 4.061
Human and Animal Cells TE-1(RCB1894) TE-8(RCB2098) TE-15(RCB1951)