Mitochondrial pyruvate carrier modulates the epithelial-mesenchymal transition in cholangiocarcinoma

Tomofumi Ohashi, Hidetoshj Eguchj, Koichi Kawamoto, Masamitsu Konno, Ayumu Asat, Hugh Colvin, Yuji Ueda, Hirofumi Takaoka, Yoshifumi Iwagami, Daisaku Yamada, Tadafumi Asaoka, Takehiro Noda, Hiroshi Wada, Kunihito Gotoh, Shogo Kobayashi, Jun Koseki, Taroh Satoh, Kazuhiko Ogawa, Yuichiro Doki, Masaki MoriHideshi Ishii

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Intrahepatic cholangiocarcinoma (ICC) is known to have a high malignant potential. Because of its high recurrence rate, ICC has a poor prognosis even after complete tumor resection. Compared with normal differentiated cells, cancer cells have an altered metabolism for supporting their survival in severe conditions. Cancer cells acquire additional malignant potential as a result of this metabolic alteration. Thus, the molecules known to be involved in cancer metabolism, could be novel therapeutic targets. The mitochondrial pyruvate carrier (MPC) is a recently discovered pyruvate transporter, which is located in the mitochondrial inner membrane. Although MPC is composed of two subunits, it has been reported that the MPC1 subunit is specifically associated with poor prognosis in several cancers, including colorectal and prostate cancer. However, only a few studies have assessed the clinical significance of MPC1 and the molecular mechanisms underlying its influence on cancer progression are not well understood. This study aimed to clarify the function of MPC1 that affects the malignant potential of ICC. The expression of MPC1 in ICC clinical specimens was determined by immunohistochemistry In addition, the correlations between MPC1 expression and the survival rate, as well as various clinicopathological parameters were assessed. Low MPC1 expression correlated with poor ICC prognosis and was correlated with tumor invasion and distant metastasis. Both these phenomena are closely associated with the epithelial-mesenchymal transition (EMT). Therefore, we investigated the impact of altering the MPC1 gene expression on the malignant potential of cancer cells using biliary tract cancer cell lines in vitro. The expression of MPC1 was downregulated in the cells induced to undergo EMT following treatment with TGF-β. Furthermore, the inhibition of MPC1 expression induced EMT in cancer cells, and the overexpression of MPC1 suppressed the migration of tumor cells. These results indicated that MPC1 could be a novel therapeutic target in some cancers.

Original languageEnglish
Pages (from-to)1276-1282
Number of pages7
JournalOncology reports
Volume39
Issue number3
DOIs
Publication statusPublished - Mar 2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Mitochondrial pyruvate carrier modulates the epithelial-mesenchymal transition in cholangiocarcinoma'. Together they form a unique fingerprint.

  • Cite this

    Ohashi, T., Eguchj, H., Kawamoto, K., Konno, M., Asat, A., Colvin, H., Ueda, Y., Takaoka, H., Iwagami, Y., Yamada, D., Asaoka, T., Noda, T., Wada, H., Gotoh, K., Kobayashi, S., Koseki, J., Satoh, T., Ogawa, K., Doki, Y., ... Ishii, H. (2018). Mitochondrial pyruvate carrier modulates the epithelial-mesenchymal transition in cholangiocarcinoma. Oncology reports, 39(3), 1276-1282. https://doi.org/10.3892/or.2017.6172