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. 2018 Dec 29:18:219.
doi: 10.1186/s12935-018-0713-x. eCollection 2018.

An actin-binding protein ESPN is an independent prognosticator and regulates cell growth for esophageal squamous cell carcinoma

Shau-Hsuan Li  1 , Hung-I Lu  2 , Wan-Ting Huang  3 , Yen-Hao Chen  1 , Chien-Ming Lo  2 , Ya-Chun Lan  1 , Wei-Che Lin  4 , Hsin-Ting Tsai  5 , Chang-Han Chen  5   6
Affiliations

An actin-binding protein ESPN is an independent prognosticator and regulates cell growth for esophageal squamous cell carcinoma

Shau-Hsuan Li et al. Cancer Cell Int. .

Abstract

Background: ESPN (Espin), an actin filament-binding protein, plays an important role in regulating the organization, dimensions, dynamics, and signaling capacities of the actin filament-rich, microvillus-type specializations that mediate sensory transduction in various mechanosensory and chemosensory cells. Recent few studies show that ESPN regulates metastasis and cell proliferation in melanoma. However, the significance of ESPN in other cancers such as esophageal squamous cell carcinoma (ESCC) remains largely unknown.

Methods: Immunohistochemistry was performed in 169 patients with ESCC and correlated with clinicopathological features and survival. The functional role of ESPN in ESCC cells was determined by ESPN-mediated siRNA.

Results: Univariate analyses showed that high ESPN expression was associated with inferior overall survival (P = 0.005) and disease-free survival (P = 0.035). High ESPN expression was an independent prognosticator in multivariate analysis for overall survival (P = 0.009, hazard ratio = 1.688) and disease-free survival (P = 0.049, hazard ratio = 1.451). The 5-year overall survival rates were 30% and 54% in patients with high and low expression of ESPN, respectively. Inhibition of endogenous ESPN in ESCC cells decreased ESCC growth by reducing cell proliferating rates.

Conclusions: High ESPN expression is independently associated with poor prognosis in patients with ESCC and downregulation of ESPN inhibits ESCC cell growth. Our results suggest that ESPN may be a novel therapeutic target for patients with ESCC.

Keywords: ESPN; Esophageal cancer; Squamous cell carcinoma.

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Figures

Fig. 1
Fig. 1
Immunohistochemical staining of ESPN in esophageal squamous cell carcinoma. A Representative example of ESPN expression with no staining. Original magnification, ×200. B Representative example of ESPN expression with weak staining. Original magnification, ×200. C Representative example of ESPN expression with moderate staining. Original magnification, ×200. D Representative example of ESPN expression with strong staining. Original magnification, ×200. E ESPN immunoreactivity was present in cells in seminiferous ducts in human testis used as a positive control. Original magnification, ×200
Fig. 2
Fig. 2
Kaplan–Meier curves according to ESPN status. a Overall survival according to ESPN status. b Disease-free survival according to ESPN status
Fig. 3
Fig. 3
Knockdown of ESPN inhibited ESCC cells growth in vitro. a, c The endogenous expression of ESPN in KYSE270 and TE10 cell lines transfected with ESPN-mediated siRNAs and negative control were determined at mRNA and protein levels by qRT-PCR and Western blotting. b, d The cell viabilities and colony numbers of the siESPN-ESCC and negative control-ESCC cells were measured in different time points as indicated by MTT assay and colony formation assay. Data from three independent experiments are expressed as mean ± SD
Fig. 4
Fig. 4
The cell cycle distribution, p21 and p27 expressions were determined in siESPN ESCC cells. a The cell cycle progression was analyzed by flow cytometry in negative control, ESPN-depleted KYSE270 and ESPN-depleted TE10 cells. b The protein expression levels of p21 and p27 were examined by Western blotting in negative control, ESPN-depleted KYSE270 and ESPN-depleted TE10 cells
See this image and copyright information in PMC

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