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 a...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.展开更多
Energy metabolism reprogramming was recently identified as one of the cancer hallmarks.One of the underlying mechanisms of energy metabolism reprogramming is mitochondrial dysfunction caused by mutations in nuclear ge...Energy metabolism reprogramming was recently identified as one of the cancer hallmarks.One of the underlying mechanisms of energy metabolism reprogramming is mitochondrial dysfunction caused by mutations in nuclear genes or mitochondrial DNA(mtDNA).In the past decades,several types of somatic mtDNA alterations have been identified in gastric cancer.However,the role of these mtDNA alterations in gastric cancer progression remains unclear.In this review,we summarize recently identified somatic mtDNA alterations in gastric cancers as well as the relationship between these alterations and the clinicopathological features of gastric cancer.The causative factors and potential roles of the somatic mtDNA alterations in cancer progression are also discussed.We suggest that point mutations and mtDNA copy number decreases are the two most common mtDNA alterations that result in mitochondrial dysfunction in gastric cancers.The two primary mutation types(transition mutations and mononucleotide or dinucleotide repeat instability)imply potential causative factors.Mitochondrial dysfunction-generated reactive oxygen species may be involved in the malignant changes of gastric cancer.The search for strategies to prevent mtDNA alterations and inhibit the mitochondrial retrograde signaling will benefit the development of novel treatments for gastric cancer and other malignancies.展开更多
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-111-007A 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
文摘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 from the Center of Excellence for Cancer Research at Taipei Veterans General,the Ministry of Health and Welfare,No.DOH102-TDC-111-007,Executive Yuana grant from the Ministry of Education,Aim for the Top University Planand grant from the National Science Council,No.NSC101-2320-B-010-068-MY3,Taiwan
文摘Energy metabolism reprogramming was recently identified as one of the cancer hallmarks.One of the underlying mechanisms of energy metabolism reprogramming is mitochondrial dysfunction caused by mutations in nuclear genes or mitochondrial DNA(mtDNA).In the past decades,several types of somatic mtDNA alterations have been identified in gastric cancer.However,the role of these mtDNA alterations in gastric cancer progression remains unclear.In this review,we summarize recently identified somatic mtDNA alterations in gastric cancers as well as the relationship between these alterations and the clinicopathological features of gastric cancer.The causative factors and potential roles of the somatic mtDNA alterations in cancer progression are also discussed.We suggest that point mutations and mtDNA copy number decreases are the two most common mtDNA alterations that result in mitochondrial dysfunction in gastric cancers.The two primary mutation types(transition mutations and mononucleotide or dinucleotide repeat instability)imply potential causative factors.Mitochondrial dysfunction-generated reactive oxygen species may be involved in the malignant changes of gastric cancer.The search for strategies to prevent mtDNA alterations and inhibit the mitochondrial retrograde signaling will benefit the development of novel treatments for gastric cancer and other malignancies.
