RRC ID 76409
Author Chao D, Ariake K, Sato S, Ohtsuka H, Takadate T, Ishida M, Masuda K, Maeda S, Miura T, Mitachi K, Yu XJ, Fujishima F, Mizuma M, Nakagawa K, Morikawa T, Kamei T, Unno M.
Title Stomatin‑like protein 2 induces metastasis by regulating the expression of a rate‑limiting enzyme of the hexosamine biosynthetic pathway in pancreatic cancer.
Journal Oncol Rep
Abstract Stomatin‑like protein 2 (SLP‑2) 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 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 conducted, while a mouse xenograft model was used to evaluate the functional role of SLP‑2 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 SLP‑2. In vitro analysis demonstrated that cells in which SLP‑2 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 SLP‑2 was increased in liver metastatic sites. Microarray analysis indicated that this protein regulated the expression of glutamine‑fructose‑6‑phosphate transaminase 2 (GFPT2), a rate‑limiting enzyme of the hexosamine biosynthesis pathway. SLP‑2 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 SLP‑2 and its downstream pathway could provide novel therapeutic targets for PC.
Volume 45(6)
Published 2021-6-1
DOI 10.3892/or.2021.8041
PII 90
PMID 33846782
PMC PMC8042670
MeSH Adult Aged Aged, 80 and over Animals Apoptosis / genetics Biosynthetic Pathways / genetics Blood Proteins / genetics Blood Proteins / metabolism* Carcinoma, Pancreatic Ductal / genetics* Carcinoma, Pancreatic Ductal / secondary Cell Line, Tumor Cell Movement / genetics Cell Proliferation / genetics Disease Progression Female Gene Expression Regulation, Neoplastic Gene Silencing Glucose / metabolism Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / genetics* Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / metabolism Hexosamines / biosynthesis* Humans Liver Neoplasms / genetics* Liver Neoplasms / secondary Male Membrane Proteins / genetics Membrane Proteins / metabolism* Mice Middle Aged Neoplasm Invasiveness / genetics Pancreatic Neoplasms / genetics* Pancreatic Neoplasms / pathology Retrospective Studies Xenograft Model Antitumor Assays
IF 3.417
Human and Animal Cells PANC-1(RCB2095)