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

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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 involve- ment 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 anal- ysis 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.

Original languageEnglish
Article number90
JournalOncology reports
Volume45
Issue number6
DOIs
Publication statusPublished - 2021 Jun

Keywords

  • Glutamine-fructose-6-phosphate transaminase 2
  • Liver metastasis
  • Pancreatic cancer
  • Stomatin-likeprotein2

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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