Up-regulation of SPOCK1 induces epithelial–mesenchymal transition and promotes migration and invasion in esophageal squamous cell carcinoma

Abstract

Invasion and metastasis are the major causes of death in patients with esophageal squamous cell carcinoma (ESCC). Recent studies have confirmed that SPARC/osteonectin, cwcv and kazal-like domains proteoglycan 1 (SPOCK1) plays multiple roles in cancer progression. This study aims to explore the clinical characteristics of SPOCK1 in ESCC and its roles in the migration and invasion of ESCC cell lines. In this study, the up-regulation of SPOCK1 expression was frequently detected in primary ESCC tumor tissues compared with those in non-tumor tissues, which was significantly associated with tumor invasion (p = 0.004) and distant metastasis (p = 0.010). SPOCK1 was expressed at higher level in TE13 cells as compared to the low malignant Eca109 and TE1 cells. Overexpression of SPOCK1 in Eca109 cells decreased the expressions of epithelial marker E-cadherin and ZO-1, while increased mesenchymal marker Vimentin and N-cadherin levels. After ectopic expression of SPOCK1, Eca109 cells exhibited a morphological change from an epithelial cobblestone phenotype to an elongated fibroblastic phenotype, concomitant with cytoskeletal rearrangements and increased migration and invasion, suggesting that EMT occurs. While silencing SPOCK1 in TE13 cells had the opposite effects. These results suggest that up-regulation of SPOCK1 in ESCC induces EMT, thus promotes migration and invasion in ESCC cells.

Stromal SPOCK1 supports invasive pancreatic cancer growth

“…Previous publications have demonstrated a role for SPOCK1 in cancer types such as breast cancer (Fan et al ., ), prostate cancer (Chen et al ., ; Yang et al ., ), glioblastomas (Yu et al ., ), urothelial carcinomas (Ma et al ., ), ovarian cancer (Zhang et al ., ), esophageal squamous cell carcinomas (Song et al ., ), gallbladder cancer (Shu et al ., ), lung cancer (Miao et al ., ), and hepatocellular carcinomas (Li et al ., ). All these studies focused on the epithelial fraction.…”

SPOCK1 Is a Novel Transforming Growth Factor-β–Induced Myoepithelial Marker That Enhances Invasion and Correlates with Poor Prognosis in Breast Cancer

“…Accumulating evidence indicates the critical role of epithelial–mesenchymal transition (EMT) in the pathogenesis of MBC [ 22 , 28 , 31 , 32 ]. Intriguingly, SPOCK1 expression has been shown to induce EMT in multiple cancer cell lines, including gall bladder, lung, and esophagus, and has been demonstrated to confer resistance to HER2 target therapy in gastric cancer cell line through EMT [ 24 – 26 , 33 ]. Thus, the enrichment of SPOCK1 expression in MBC and the correlation between SPOCK1 expression and triple-negative or basal-like IDC that have been shown to preferentially express EMT markers [ 34 ] provide in vivo evidence for an association between SPOCK1 and the EMT, and support such an association being present in cell lines.…”

A Genome-Wide Association Study Identifies Genetic Variants Associated with Mathematics Ability

“…In hepatocellular carcinoma and gallbladder cancer, elevated expression of SPOCK1 resulted in activation ofPI3K/AKT signaling which could block apoptosis and promote proliferation, invasiveness and metastasis of cancer cells 16 17 . In addition, increased expression of SPOCK1 was implicated in epithelial-to-mesenchymal transition (EMT) which promoted migration and invasion in lung cancer and esophageal squamous cell carcinoma and conferred acquired drug resistance in gastric cancer 18 19 20 . Therefore, SPOCK1 has been considered as a novel prognostic and therapeutic target for various cancer types.…”