TY - JOUR
T1 - Mitochondrial pyruvate carrier modulates the epithelial-mesenchymal transition in cholangiocarcinoma
AU - Ohashi, Tomofumi
AU - Eguchj, Hidetoshj
AU - Kawamoto, Koichi
AU - Konno, Masamitsu
AU - Asat, Ayumu
AU - Colvin, Hugh
AU - Ueda, Yuji
AU - Takaoka, Hirofumi
AU - Iwagami, Yoshifumi
AU - Yamada, Daisaku
AU - Asaoka, Tadafumi
AU - Noda, Takehiro
AU - Wada, Hiroshi
AU - Gotoh, Kunihito
AU - Kobayashi, Shogo
AU - Koseki, Jun
AU - Satoh, Taroh
AU - Ogawa, Kazuhiko
AU - Doki, Yuichiro
AU - Mori, Masaki
AU - Ishii, Hideshi
N1 - Funding Information:
We wish to thank the members of our laboratories for their fruitful discussions. In addition, this study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology (K.O., Y.d., M.M., and h.I.); a Grant-in-Aid from the Ministry of health, Labor and Welfare (K.O., Y.d., M.M., and h.I.); a grant from P-dIRECT (h.I.); a grant from the National Institute of Biomedical Innovation (M.M. and h.I.); and a grant from Osaka University drug discovery Funds (M.M. and h.I.).
PY - 2018/3
Y1 - 2018/3
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85041724521&partnerID=8YFLogxK
U2 - 10.3892/or.2017.6172
DO - 10.3892/or.2017.6172
M3 - Article
C2 - 29286150
AN - SCOPUS:85041724521
VL - 39
SP - 1276
EP - 1282
JO - Oncology Reports
JF - Oncology Reports
SN - 1021-335X
IS - 3
ER -
