Stomatin-like protein 2 induces metastasis by regulating the expression of a rate-limiting enzyme of the hexosamine biosynthetic pathway in pancreatic cancer
Autor: | Kei Nakagawa, Kunihiro Masuda, Fumiyoshi Fujishima, Takayuki Miura, Tatsuyuki Takadate, Takanori Morikawa, Xun Jing Yu, Kyohei Ariake, Katsutaka Mitachi, Hideo Ohtsuka, Masaharu Ishida, S. Sato, Shimpei Maeda, Takashi Kamei, Michiaki Unno, Dang Chao, Masamichi Mizuma |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Male Cancer Research Glucose uptake Cell pancreatic cancer Apoptosis Metastasis stomatin-like protein 2 Mice 0302 clinical medicine Cell Movement Aged 80 and over Chemistry Liver Neoplasms General Medicine Articles Blood Proteins Cell cycle Middle Aged Gene Expression Regulation Neoplastic medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Disease Progression Female Carcinoma Pancreatic Ductal Adult 03 medical and health sciences glutamine-fructose-6-phosphate transaminase 2 Pancreatic cancer Cell Line Tumor medicine Animals Humans Neoplasm Invasiveness Gene Silencing Aged Cell Proliferation Retrospective Studies Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) Oncogene Microarray analysis techniques Cell growth Membrane Proteins Hexosamines medicine.disease Xenograft Model Antitumor Assays Biosynthetic Pathways Pancreatic Neoplasms liver metastasis 030104 developmental biology Glucose Cancer research |
Zdroj: | Oncology Reports |
ISSN: | 1791-2431 1021-335X |
Popis: | 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. |
Databáze: | OpenAIRE |
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