Stomatin-like protein 2 induces metastasis by regulating the expression of a rate-limiting enzyme of the hexosamine biosynthetic pathway in pancreatic cancer

Stomatin-like protein 2 (SLP-2) is associated with poor prognosis in several types of cancer, including pancreatic cancer; however, the molecular mechanism of its involvement remains elusive. This study aimed to elucidate the role of this protein in the development of pancreatic cancer. Human pancreatic cancer cell lines AsPC-1 and PANC-1 were transfected by a vector expressing SLP-2 shRNA. Analyses of cell proliferation, migration, invasion, chemosensitivity, and glucose uptake were performed, while a mouse xenograft model was used to evaluate the functional role of SLP-2 in pancreatic cancer. Immunohistochemical analysis was retrospectively performed on human tissue samples to compare expression between the primary site (n=279) and the liver metastatic site (n=22). Furthermore, microarray analysis was conducted to identify genes correlated with SLP-2. In vitro analysis demonstrated that cells in which SLP-2 was suppressed showed reduced cell motility and glucose uptake, while in vivo analysis showed a dramatic decrease in the number of liver metastases. Immunohistochemistry revealed that SLP-2 was elevated in liver metastatic sites. Microarray analysis indicated this protein regulated the expression of glutamine-fructose-6-phosphate transaminase 2 (GFPT2), a rate-limiting enzyme of the hexosamine biosynthesis pathway. SLP-2 contributes to the malignant character of pancreatic cancer by inducing liver metastasis. Cell motility and glucose uptake may be induced via the hexosamine biosynthesis pathway, through the expression of GFPT2. This reveals a new mechanism of liver metastasis and implies that SLP-2 and its downstream pathway could provide novel therapeutic targets for pancreatic cancer. This study aimed to elucidate the role of SLP-2 in the development of pancreatic cancer. Human pancreatic cancer cell lines AsPC-1 were transfected by a vector expressing SLP-2 shRNA. Microarray analysis was conducted to identify genes between SLP-2 control cells (AsPC-1cont) and ASPC-1 SLP-2 suppressed cells (AsPC-1sh1, AsPC-1sh2).