Gastric cancer (GC) is a common and lethal cancer over the world [
1], with marked morbidity and mortality in China [
2]. In spite of some developments in the treatment of GC, the overall survival of GC patients remains poor because most GC patients have local and distant metastases at diagnosis [
3‐
5]. Thus, it is of vital importance to investigate the molecular mechanisms underlying metastasis to provide novel biomarkers for treatment of GC.
Tumor growth and metastasis require a series of events within the tumor microenvironment, which involve proliferation, loss of cellular adhesion, degradation of the extracelluar matrix, invasion into host stroma, cell migration, and angiogenesis [
6,
7]. Epithelial-to-mesenchymal transition (EMT) is a key event in tumor aggression and metastasis [
8]. At molecular level of EMT, cancer cells lose their cell-to-cell contacts by inhibiting the epithelial marker E-cadherin and acquiring the mesenchymal markers like N-cadherin and vimentin [
9]. However, the mechanisms and pathways underlying EMT in cancers are not comprehensively understood [
10].
Stress-Inducible Protein-1 (STIP1), initially reported as a co-chaperone that associates directly with Hsp70/Hsp90 heat shock proteins, participates in a large number of cellular processes such as RNA splicing, transcription, viral replication, protein folding and translocation, signal transduction, and cell cycle regulation [
11]. STIP1 was previously considered to be a protein functioning in intracellular compartments as it lacks transmembrane domain or signal peptide [
12]. However, studies indicate that STIP1 could be secreted out of the cells, and then bound to prion protein on cell surface and transduced signals to affect cell proliferation and apoptosis [
13‐
15]. In the last decade, a large number of functions of STIP1 have been reported, which includes the protection of cells in the nervous system, development, cellular maintenance, and tumor proliferation [
16].
STIP1 is located at 11q13, and copy number gain of this region has been found in cancers and linked to poor prognosis [
17‐
20]. STIP1 has been reported to be up-regulated in various types of cancer, including hepatocellular carcinoma [
21], pancreatic cancer [
22], ovarian cancer [
23,
24], colon cancer [
25], and cholangiocellular carcimoma [
26]. Whether STIP1 involved in the regulation of GC metastasis remains unknown. In the present study, we have sought to investigate the roles of STIP1 on migration and invasion of GC cells through both in vitro and in vivo experiments, and further explored the potential mechanism.