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
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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