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In recent decades, the multi-functional protein nucleolin (NCL) has been reported to express outside the nucleus of many cancer cells. However, the expression and role of the extra-nuclear NCL in esophageal squamous cell carcinoma (ESCC) were not well characterized. Here, NCL was detected by immunohistochemistry and Western blotting in 60 ESCC tissues. Further, the associations of NCL, EGFR, CXCR4 and Ki67 were analyzed by in vitro assays. Our results showed that NCL expression in all 40 cases of ESCC tissues with metastasis was extensively located in the nucleus, cytoplasm and cell membrane (extra-nucleus), while NCL expression in all 20 cases of ESCC without metastasis was merely limited into the nucleus (intra-nucleus).The extra-nuclear NCL expression was positively correlated with the expression of EGFR, CXCR4 and Ki67 and serves as an independent prognostic factor for ESCC patients. In vitro, NCL siRNA (si-NCL) efficaciously affected the expression of EGF or SDF-1-induced p-AKT, p-ERK and Ki67. Also, NCL siRNA inhibited the capacity of migration and invasion of ECA109 cells. In conclusions, our study suggests that NCL is implicated in the initiation and transduction of EGFR and CXCR4 signaling and further up-regulates Ki67 expression to modulate the biological behaviors of ESCC. Clinically, the extra-nuclear NCL expression can be used as an important indicator to determine metastasis and predict the prognosis, which help develop new therapeutic strategies against ESCC.

Background: Gastric tumors generally have a poor prognosis and molecular markers to improve early detection and predict outcomes are greatly needed. The present study reports that periostin (POSTN), a secretory protein that can alter the remodeling of the extracellular matrix, is highly expressed in gastric tumors.Materials and Methods: Gastric tissues were collected from patients at the Southern Medical University. These patients provided an informed consent and were approved by the institute. Normal, cancer, and metastatic gastric tissues from lymph nodes and tissues adjacent to the tumor were collected from patients diagnosed with gastric cancer. Results: Periostin expression gradually increased as the risk grade of the NIH classification increased, and this was closely correlated with disease-free survival and overall survival. Compared with adjacent normal gastric mucosa tissues, protein expression of POSTN in gastric cancer tissues and metastases was significantly higher by immunohistochemistry and Western blot analysis. In addition, POSTN was upregulated in advanced gastric cancer tissues than in early gastric cancer tissues.Moreover, the ectopic expression of POSTN in the immortalized human gastric cell line could increase the metastasis and invasion of gastric cancer cells. Conclusion: The present results could establish the significance of POSTN in driving oncogenesis and metastasis in gastric tumors, with implications for its potential use as a diagnostic or prognostic biomarker, and as a candidate therapeutic target. K E Y W O R D Sbiomarker, gastric tumors, invasion, metastasis, periostin