Open Access

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

  • Authors:
    • Dang Chao
    • Kyohei Ariake
    • Satoko Sato
    • Hideo Ohtsuka
    • Tatsuyuki Takadate
    • Masaharu Ishida
    • Kunihiro Masuda
    • Shimpei Maeda
    • Takayuki Miura
    • Katsutaka Mitachi
    • Xun Jing Yu
    • Fumiyoshi Fujishima
    • Masamichi Mizuma
    • Kei Nakagawa
    • Takanori Morikawa
    • Takashi Kamei
    • Michiaki Unno
  • View Affiliations

  • Published online on: April 5, 2021     https://doi.org/10.3892/or.2021.8041
  • Article Number: 90
  • Copyright: © Chao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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 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.
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June-2021
Volume 45 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Chao D, Ariake K, Sato S, Ohtsuka H, Takadate T, Ishida M, Masuda K, Maeda S, Miura T, Mitachi K, Mitachi K, et al: Stomatin‑like protein 2 induces metastasis by regulating the expression of a rate‑limiting enzyme of the hexosamine biosynthetic pathway in pancreatic cancer. Oncol Rep 45: 90, 2021.
APA
Chao, D., Ariake, K., Sato, S., Ohtsuka, H., Takadate, T., Ishida, M. ... Unno, M. (2021). Stomatin‑like protein 2 induces metastasis by regulating the expression of a rate‑limiting enzyme of the hexosamine biosynthetic pathway in pancreatic cancer. Oncology Reports, 45, 90. https://doi.org/10.3892/or.2021.8041
MLA
Chao, D., Ariake, K., Sato, S., Ohtsuka, H., Takadate, T., Ishida, M., Masuda, K., Maeda, S., Miura, T., Mitachi, K., Yu, X. J., Fujishima, F., Mizuma, M., Nakagawa, K., Morikawa, T., Kamei, T., Unno, M."Stomatin‑like protein 2 induces metastasis by regulating the expression of a rate‑limiting enzyme of the hexosamine biosynthetic pathway in pancreatic cancer". Oncology Reports 45.6 (2021): 90.
Chicago
Chao, D., Ariake, K., Sato, S., Ohtsuka, H., Takadate, T., Ishida, M., Masuda, K., Maeda, S., Miura, T., Mitachi, K., Yu, X. J., Fujishima, F., Mizuma, M., Nakagawa, K., Morikawa, T., Kamei, T., Unno, M."Stomatin‑like protein 2 induces metastasis by regulating the expression of a rate‑limiting enzyme of the hexosamine biosynthetic pathway in pancreatic cancer". Oncology Reports 45, no. 6 (2021): 90. https://doi.org/10.3892/or.2021.8041