摘要
Hepatocellular carcinoma(HCC)is one of the most common malignancies and is ranked third in mortality among cancer-related diseases.Mitochondria are intracellular organelles that are responsible for energy metabolism and cellular homeostasis,and mitochondrial dysfunction has been regarded as a hallmark of cancer.Over the past decades,several types of mitochondrial DNA(mtDNA)alterations have been identified in human cancers,including HCC.However,the role of these mtDNA alterations in cancer progression is unclear.In this review,we summarize the recent findings on the somatic mtDNA alterations identified in HCC and their relationships with the clinicopathological features of HCC.Recent advances in understanding the potential roles of somatic mtDNA alterations in the progression of HCC are also discussed.We suggest that somatic mtDNA mutations and a decrease in the mtDNA copy number are common events in HCC and that a mitochondrial dysfunction-activated signaling cascade may play an important role in the progression of HCC.Elucidation of the retrograde signaling pathways in HCC and the quest for strategies to block some of these pathways will be instrumental for the development of novel treatments for this and other malignancies.
Hepatocellular carcinoma (HCC) is one of the most common malignancies and is ranked third in mortality among cancer-related diseases. Mitochondria are intracellular organelles that are responsible for energy metabolism and cellular homeostasis, and mitochondrial dysfunction has been regarded as a hallmark of cancer. Over the past decades, several types of mitochondrial DNA (mtDNA) alterations have been identified in human cancers, including HCC. However, the role of these mtDNA alterations in cancer progression is unclear. In this review, we summarize the recent findings on the somatic mtDNA alterations identified in HCC and their relationships with the clinicopathological features of HCC. Recent advances in understanding the potential roles of somatic mtDNA alterations in the progression of HCC are also discussed. We suggest that somatic mtDNA mutations and a decrease in the mtDNA copy number are common events in HCC and that a mitochondrial dysfunction-activated signaling cascade may play an important role in the progression of HCC. Elucidation of the retrograde signaling pathways in HCC and the quest for strategies to block some of these pathways will be instrumental for the development of novel treatments for this and other malignancies.
基金
Supported by A Grant for the Center of Excellence for Cancer Research at Taipei Veterans General Hospital from the Ministry of Health and Welfare of the Executive Yuan,No.DOH102TDC-111-007
A Grant from the Aim for the Top University Plan of the Ministry of Education and grants from the National Science Council of Taiwan,No.NSC101-2320-B-010-068-MY3 and No.NSC100-2320-B-010-024-MY3
