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01.12.2015 | Translational Research and Biomarkers

Nuclear PROX1 is Associated with Hypoxia-Inducible Factor 1α Expression and Cancer Progression in Esophageal Squamous Cell Carcinoma

verfasst von: Takehiko Yokobori, MD, PhD, Pinjie Bao, MSc, Minoru Fukuchi, MD, PhD, Bolag Altan, MD, PhD, Daigo Ozawa, MD, PhD, Susumu Rokudai, PhD, Tuya Bai, MSc, Yuji Kumakura, MD, Hiroaki Honjo, MD, Keigo Hara, MD, Makoto Sakai, MD, PhD, Makoto Sohda, MD, PhD, Tatsuya Miyazaki, MD, PhD, Munenori Ide, MD, PhD, Masahiko Nishiyama, MD, PhD, Tetsunari Oyama, MD, PhD, Hiroyuki Kuwano, MD, PhD, FACS

Erschienen in: Annals of Surgical Oncology | Sonderheft 3/2015

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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.

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Titel: Nuclear PROX1 is Associated with Hypoxia-Inducible Factor 1α Expression and Cancer Progression in Esophageal Squamous Cell Carcinoma
verfasst von: Takehiko Yokobori, MD, PhD
Pinjie Bao, MSc
Minoru Fukuchi, MD, PhD
Bolag Altan, MD, PhD
Daigo Ozawa, MD, PhD
Susumu Rokudai, PhD
Tuya Bai, MSc
Yuji Kumakura, MD
Hiroaki Honjo, MD
Keigo Hara, MD
Makoto Sakai, MD, PhD
Makoto Sohda, MD, PhD
Tatsuya Miyazaki, MD, PhD
Munenori Ide, MD, PhD
Masahiko Nishiyama, MD, PhD
Tetsunari Oyama, MD, PhD
Hiroyuki Kuwano, MD, PhD, FACS
Publikationsdatum: 01.12.2015
Verlag: Springer US
Erschienen in: Annals of Surgical Oncology / Ausgabe Sonderheft 3/2015
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-015-4831-6

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Abstract

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Methods

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