Mitochondrial pyruvate carrier 1 functions as a tumor suppressor and predicts the prognosis of human renal cell carcinoma

Invasion and subsequent metastasis are major characteristics of malignant human renal cell carcinoma (RCC), though the mechanisms remain elusive. Mitochondrial pyruvate carrier (MPC), a key factor that controls pyruvate transportation in mitochondria, is frequently dysregulated in tumor cells and lo...

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Bibliographic Details
Published in:Laboratory investigation 2019-02, Vol.99 (2), p.191-199
Main Authors: Tang, Xiao-Peng, Chen, Qian, Li, Yi, Wang, Yan, Zou, Hong-Bo, Fu, Wen-Juan, Niu, Qin, Pan, Qian-Guang, Jiang, Pei, Xu, Xiao-Song, Zhang, Ke-Qin, Liu, Hong, Bian, Xiu-Wu, Wu, Xiong-Fei
Format: Article
Language:English
Subjects:
Animals
Antitumor activity
Biomarkers
Carcinoma, Renal Cell - diagnosis
Carcinoma, Renal Cell - metabolism
Cell Hypoxia
Cell Line
Female
Gelatinase B
Humans
Hypoxia
Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
In vivo methods and tests
Kidney - metabolism
Kidney cancer
Kidney Neoplasms - diagnosis
Kidney Neoplasms - metabolism
Matrilysin
Matrix Metalloproteinases - analysis
Matrix Metalloproteinases - metabolism
Medical prognosis
Metastases
Mice
Mice, SCID
Mitochondria
Mitochondrial Membrane Transport Proteins - analysis
Mitochondrial Membrane Transport Proteins - metabolism
Monocarboxylic Acid Transporters
Neoplasms, Experimental
Patients
Prognosis
Pyruvic acid
Renal cell carcinoma
Survival
Tissues
Tumor cells
Tumor suppressor genes
Tumors
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Summary:Invasion and subsequent metastasis are major characteristics of malignant human renal cell carcinoma (RCC), though the mechanisms remain elusive. Mitochondrial pyruvate carrier (MPC), a key factor that controls pyruvate transportation in mitochondria, is frequently dysregulated in tumor cells and loss of MPC predicts poor prognosis in various types of cancer. However, the clinical relevance and functional significance of MPC in RCC remain to be elucidated. In this study, we investigated the expression of MPC1 and MPC2 in specimens from RCC patients and observed downregulation of MPC1, but not MPC2, in RCC tissues compared with adjacent non-cancerous tissue. Moreover, RCC patients with higher MPC1 expression exhibited longer overall survival rate than those with lower MPC1. Functionally, MPC1 suppressed the invasion of RCC cells in vitro and reduced the growth of RCC cells in vivo, possibly through inhibition of MMP7 and MMP9. Further studies revealed that loss of MPC1 was induced by hypoxia in RCC cells, and notably, MPC1 expression, was negatively correlated with HIF1α expression in RCC cells and patient samples. Taken together, our results identify anti-tumor function of MPC1 in RCC and revealed MPC1 as a novel prognostic biomarker to predict better patient survival. Mitochondrial pyruvate carrier1 (MPC1) is a key factor that controls pyruvate transportation in mitochondria. Renal cell carcinoma (RCC) patients with higher MPC1 expression in tumors exhibit longer overall survival rate than those with lower MPC1. This study shows that MPC1 is a novel prognostic biomarker to predict patient.
ISSN:0023-6837
1530-0307
DOI:10.1038/s41374-018-0138-0