RESUMO
Stomatinlike protein 2 (SLP2) is associated with poor prognosis in several types of cancer, including pancreatic cancer (PC); however, the molecular mechanism of its involvement remains elusive. The present study aimed to elucidate the role of this protein in the development of PC. Human PC cell lines AsPC1 and PANC1 were transfected by a vector expressing SLP2 shRNA. Analyses of cell proliferation, migration, invasion, chemosensitivity, and glucose uptake were conducted, while a mouse xenograft model was used to evaluate the functional role of SLP2 in PC. 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 the genes correlated with SLP2. In vitro analysis demonstrated that cells in which SLP2 was suppressed exhibited reduced cell motility and glucose uptake, while in vivo analysis revealed a marked decrease in the number of liver metastases. Immunohistochemistry revealed that SLP2 was increased in liver metastatic sites. Microarray analysis indicated that this protein regulated the expression of glutaminefructose6phosphate transaminase 2 (GFPT2), a ratelimiting enzyme of the hexosamine biosynthesis pathway. SLP2 contributed to the malignant character of PC by inducing liver metastasis. Cell motility and glucose uptake may be induced via the hexosamine biosynthesis pathway through the expression of GFPT2. The present study revealed a new mechanism of liver metastasis and indicated that SLP2 and its downstream pathway could provide novel therapeutic targets for PC.