Protein-Tyrosine Phosphatase 1B Contributes to Calreticulin-Induced Cell Migration and Metastasis of Esophageal Squamous Cell Carcinoma
Menée in vitro, à l'aide de xénogreffes et à partir d'échantillons tumoraux prélevés sur des patients atteints d'un carcinome épidermoïde de l'œsophage, cette étude met en évidence des mécanismes par lesquels, en régulant la signalisation de la calréticuline (une protéine chaperon), l'enzyme PTP1B favorise le processus métastatique
Calreticulin (CRT) is a Ca2+-binding protein that alters Ca2+-homeostasis in the endoplasmic reticulum (ER) by acting as a chaperone in cells. We previously showed that CRT was overexpressed in esophageal squamous cell carcinoma (ESCC), and elevated CRT expression promoted the migration and invasion of ESCC cells. In the present study, we investigate the mechanisms underlying role of CRT in esophageal carcinoma progression. We found that depletion of CRT or protein-tyrosine phosphatase 1B (PTP1B) reduced ESCC cell migration and metastasis to the lung, while restoration of PTP1B protein levels rescued cell migration in CRT-silenced cells. Knock-down of CRT decreased PTP1B protein expression by reducing phosphorylation at the Y694 site of Stat5a, while knock-down of PTP1B reduced Erk1/2 phosphorylation at T204. Immunohistochemical analysis of CRT and PTP1B expression in ESCC patient tissues revealed that their expressions were correlated. PTP1B expression was also associated with poor survival in patients with CRT overexpression. Overall, our data indicate a novel signaling pathway connecting CRT, Stat5a, PTP1B and Erk1/2 in the regulation of ESCC cell migration. These findings suggest that PTP1B is a downstream effector of CRT signaling that promotes ESCC progression and can potentially be used as a new drug target.