Hypoxia inducible factors in hepatocellular carcinoma

Chen, Chu; Lou, Tao

doi:10.18632/oncotarget.17358

Cited by 119 publications

(136 citation statements)

References 125 publications

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“…However, for patients often diagnosed with advanced, unresectable or metastatic HCC, chemotherapeutic treatment would be the only option [1] . Yet, as reported, significant drug resistance in these patients ultimately resulted in treatment failure [6] .…”

Section: Introductionmentioning

confidence: 85%

“…Through various signaling pathways, hypoxia further triggers a series of HCC transformation, mediating its angiogenesis, metastasis, metabolism deregulation and drug resistance [6] . Hypoxia is a major cause of hypervasculature of HCC by inducing angiogenic factors to stimulate angiogenesis and support tumor growth [15] .…”

Section: Hypoxia Plays Critical Roles In the Progression And Malignanmentioning

confidence: 99%

“…The complicated and sophisticated pathways underlying hypoxia have been extensively investigated, and HIFs are identified to play pivotal roles under hypoxia, which has attracted most attention in this field for the last decades [6,8] . Yet recently, the findings on the HIFs-independent regulation of tumor angiogenesis and chemoresistance under hypoxic conditions have challenged this notion and raised the possibility that the other important signaling pathways may also participate and promote the progression and malignance of HCC [10][11][12][13][14] .…”

Section: Molecular Pathways Involved In Hypoxic Hcc Malignancementioning

confidence: 99%

“…Hypoxia is a common phenomenon in the intratumor regions of HCC patients [6] . Abnormal microvasculature and unrestrained proliferation of HCC cells lead to oxygen deficiency [6,7] .…”

Section: Introductionmentioning

confidence: 99%

“…Abnormal microvasculature and unrestrained proliferation of HCC cells lead to oxygen deficiency [6,7] . Hypoxia is involved in multiple biological process of HCC and promotes tumor aggressiveness, chemoresistance and immunotherapy resistance [8,9] .…”

Section: Introductionmentioning

confidence: 99%

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Hypoxic microenvironment and hepatocellular carcinoma treatment

Lin¹,

Chang²,

Zhu³

et al. 2018

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Hepatocellular carcinoma (HCC) is one of the most rapidly growing and prevalent cancers in the whole world. The characterized hypoxia region inside the HCC tumors has been recently found as the key driver of HCC malignance and treatment failure, leading to a variety of hypoxia-related biological consequences including angiogenesis, metastasis, metabolism deregulation and drug resistance, which ultimately resulted in treatment failure of HCC. This review will summarize the signaling pathways involved in hypoxia-mediated malignance of HCC and discuss current advances of hypoxia-targeted therapies.

show abstract

Section: Introductionmentioning

confidence: 85%

Section: Hypoxia Plays Critical Roles In the Progression And Malignanmentioning

confidence: 99%

Section: Molecular Pathways Involved In Hypoxic Hcc Malignancementioning

confidence: 99%

“…Hypoxia is a common phenomenon in the intratumor regions of HCC patients [6] . Abnormal microvasculature and unrestrained proliferation of HCC cells lead to oxygen deficiency [6,7] .…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Hypoxic microenvironment and hepatocellular carcinoma treatment

Lin¹,

Chang²,

Zhu³

et al. 2018

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Mitochondrial protein import dysfunction: mitochondrial disease, neurodegenerative disease and cancer

2021

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The majority of proteins localised to mitochondria are encoded by the nuclear genome, with approximately 1500 proteins imported into mammalian mitochondria. Dysfunction in this fundamental cellular process is linked to a variety of pathologies including neuropathies, cardiovascular disorders, myopathies, neurodegenerative diseases and cancer, demonstrating the importance of mitochondrial protein import machinery for cellular function. Correct import of proteins into mitochondria requires the co‐ordinated activity of multimeric protein translocation and sorting machineries located in both the outer and inner mitochondrial membranes, directing the imported proteins to the destined mitochondrial compartment. This dynamic process maintains cellular homeostasis, and its dysregulation significantly affects cellular signalling pathways and metabolism. This review summarises current knowledge of the mammalian mitochondrial import machinery and the pathological consequences of mutation of its components. In addition, we will discuss the role of mitochondrial import in cancer, and our current understanding of the role of mitochondrial import in neurodegenerative diseases including Alzheimer's disease, Huntington's disease and Parkinson's disease.

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3D High‐Content Culturing and Drug Screening Platform to Study Vascularized Hepatocellular Carcinoma in Hypoxic Condition

Lim

Choi

Ahn

et al. 2021

Advanced NanoBiomed Research

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Hypoxia in the tumor microenvironment (TME) is the leading cause of metastasis and chemoresistance in cancer cells. Numerous 3D in vitro models have been proposed to study hypoxic stress, but none have enabled sufficient analysis of hepatocellular carcinoma (HCC). Herein, a 3D in vitro tumor vasculature model for HCC is introduced to investigate cellular responses and drug resistance under hypoxic conditions through high‐content screening. The hypoxic TME of vascularized HCC can be established by maintaining the platform in a hypoxia chamber and is used to analyze the diverse physiological responses of the TME to normoxia, hypoxia, and drug treatment. The proposed platform also demonstrates the hypoxic status naturally induced by 3D HCC spheroids for comparison with single HCC cells cultured in the hypoxia chamber. The results show that hypoxic stress in the HCC vasculature promotes angiogenesis, hypoxia‐inducible factor 1 (HIF‐1) expression, and proliferation; it also enhances drug resistance. The hypoxic tumor vasculature of the model generates cellular responses that are also expressed in the physiological hypoxic microenvironment of HCC. These findings suggest that our high‐content microfluidic platform can be applied as a powerful tool to develop anticancer therapeutics, which have remained elusive because of hypoxia in the TME.

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Hypoxia inducible factors in hepatocellular carcinoma

Cited by 119 publications

References 125 publications

Hypoxic microenvironment and hepatocellular carcinoma treatment

Hypoxic microenvironment and hepatocellular carcinoma treatment

Mitochondrial protein import dysfunction: mitochondrial disease, neurodegenerative disease and cancer

3D High‐Content Culturing and Drug Screening Platform to Study Vascularized Hepatocellular Carcinoma in Hypoxic Condition

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