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conferenceseries
.com
Volume 9, Issue 9 (Suppl)
J Cancer Sci Ther, an open access journal
ISSN: 1948-5956
World Cancer 2017
October 19-21, 2017
25
th
WORLD CANCER CONFERENCE
October 19-21, 2017 | Rome, Italy
Decrease in expression of the mitoribosomal subunit, MRPL13, enhances hepatoma cell invasiveness
via elevated claudin-1
Young-Kyoung Lee, Jin J Lim
and
Gyesoon Yoon
Ajou University School of Medicine, South Korea
I
mpaired mitochondrial oxidative phosphorylation (OXPHOS) capacity, accompanied by enhanced glycolysis, is a key
metabolic feature of cancer cells, but its underlying mechanism remains unclear. Previously, we reported that human
hepatoma cells that harbor OXPHOS defects exhibit high tumor cell invasiveness via elevated claudin-1 (CLN1). In the
present study, we show that OXPHOS-defective hepatoma cells (SNU354 and SNU423 cell lines) exhibit reduced expression of
mitochondrial ribosomal protein L13 (MRPL13), a mitochondrial ribosome (mitoribosome) subunit, suggesting a ribosomal
defect. Specific mitoribosomal translation inhibition with doxycycline and chloramphenicol, or siRNA-mediated MRPL13
knockdown decreased mitochondrial protein expression, reduced the oxygen consumption rate (OCR), and increased CLN1-
mediated tumor cell invasiveness in SNU387 cells, which have active mitochondria. Interestingly, we also found that exogenous
lactate treatment suppressed MRPL13 expression and OCR, and induced CLN1 expression. A bioinformatics analysis of the
open RNA-Seq database from The Cancer Genome Atlas Liver Hepatocellular carcinoma (TCGA-LIHC) cohort disclosed
a significant negative correlation between MRPL13 and CLN1 expression. Moreover, in LIHC patients with low MRPL13
expression, two oxidative metabolic indicators, pyruvate dehydrogenase B expression and the ratio of lactate dehydrogenase
(LDH) type B to LDH type A, significantly and negatively correlated with CLN1 expression. This observation implied that
the combination of elevated glycolysis and deficient MRPL13 activity is negatively linked to CLN1-mediated tumor activity
in LIHC. These results suggest that OXPHOS defects may be initiated and propagated by lactate-mediated mitoribosomal
deficiencies and that these deficiencies are critically involved in LIHC development.
Biography
Young-Kyoung Lee received her PhD in Biochemistry from Ajou University School of Medicine, Suwon, Korea. She is working as a Post-Doctoral Research Fellow
at Ajou University School of Medicine. For about last ten years, her research has been focused on elucidation of molecular mechanisms of mitochondrial respiratory
defects which are often observed in cancer, the retrograde signaling triggered by the respiratory defect and its relevance to cancer activities.
algamsa109@naver.comYoung-Kyoung Lee et al., J Cancer Sci Ther 2017, 9:9(Suppl)
DOI: 10.4172/1948-5956-C1-112