The Role of IGF/IGF-1R Signaling in Hepatocellular Carcinomas: Stemness-Related Properties and Drug Resistance

Insulin-like Growth Factor (IGF)/IGF-1 Receptor (IGF-1R) signaling is known to regulate stem cell pluripotency and differentiation to trigger cell proliferation, organ development, and tissue regeneration during embryonic development. Unbalanced IGF/IGF-1R signaling can promote cancer cell prolifera...

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Published in:International journal of molecular sciences 2021-02, Vol.22 (4), p.1931
Main Authors: Ngo, Mai-Huong Thi, Jeng, Han-Yin, Kuo, Yung-Che, Diony Nanda, Josephine, Brahmadhi, Ageng, Ling, Thai-Yen, Chang, Te-Sheng, Huang, Yen-Hua
Format: Article
Language:English
Subjects:
Carcinoma, Hepatocellular - complications
Carcinoma, Hepatocellular - drug therapy
Carcinoma, Hepatocellular - metabolism
Cytokines - metabolism
Drug Resistance, Neoplasm - drug effects
Hepatitis B - complications
Hepatitis B - metabolism
Hepatitis B - virology
Hepatitis B virus - physiology
Humans
Liver Neoplasms - complications
Liver Neoplasms - drug therapy
Liver Neoplasms - metabolism
Molecular Targeted Therapy - methods
Neoplasm Recurrence, Local
Protein Kinase Inhibitors - pharmacology
Protein Kinase Inhibitors - therapeutic use
Receptor, IGF Type 1 - antagonists & inhibitors
Receptor, IGF Type 1 - metabolism
Review
Signal Transduction
Somatomedins - metabolism
Virus Replication
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Summary:Insulin-like Growth Factor (IGF)/IGF-1 Receptor (IGF-1R) signaling is known to regulate stem cell pluripotency and differentiation to trigger cell proliferation, organ development, and tissue regeneration during embryonic development. Unbalanced IGF/IGF-1R signaling can promote cancer cell proliferation and activate cancer reprogramming in tumor tissues, especially in the liver. Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death, with a high incidence and mortality rate in Asia. Most patients with advanced HCC develop tyrosine kinase inhibitor (TKI)-refractoriness after receiving TKI treatment. Dysregulation of IGF/IGF-1R signaling in HCC may activate expression of cancer stemness that leads to TKI refractoriness and tumor recurrence. In this review, we summarize the evidence for dysregulated IGF/IGF-1R signaling especially in hepatitis B virus (HBV)-associated HCC. The regulation of cancer stemness expression and drug resistance will be highlighted. Current clinical treatments and potential therapies targeting IGF/IGF-1R signaling for the treatment of HCC will be discussed.
ISSN:1422-0067
1422-0067
DOI:10.3390/ijms22041931