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Link et al. Hepatoma Res 2017;3:95-104 Hepatoma Research
DOI: 10.20517/2394-5079.2017.07
www.hrjournal.net
Review Open Access

Roles of p53 in extrinsic factor-induced

liver carcinogenesis

Tim Link, Tomoo Iwakuma

Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Correspondence to: Dr. Tomoo Iwakuma, Department of Cancer Biology, University of Kansas Medical Center, 3901 Rainbow Blvd., Wahl Hall East
2005, Kansas City, KS 66160, USA. E-mail: tiwakuma@kumc.edu
How to cite this article: Link T, Iwakuma T. Roles of p53 in extrinsic factor-induced liver carcinogenesis. Hepatoma Res 2017;3:95-104.

Dr. Tomoo Iwakuma, M.D., Ph.D., is an associate professor in the Department of Cancer Biology at the University
of Kansas Medical Center (KUMC). Dr. Iwakuma received his M.D. at Kyushu University in Japan, majoring in
orthopedics in 1991. He also received his Ph.D. at the Department of Biochemistry at the same university in 1997. He
spent several years as a research fellow studying gene therapy, pharmacology, and molecular genetics in different
laboratories. Following postdoctoral training at the Department of Molecular Genetics at the University of Texas M.D.
Anderson Cancer Center, he joined Louisiana State University Health Sciences Center in the Department of Genetics
as an assistant professor on August 15, 2005. On August 1, 2011, he transitioned to KUMC as an associate professor.
Dr. Iwakuma’s primary research focuses on the field of cancer research, specifically on cancer progression and
metastasis in bone and soft tissue sarcoma, head and neck squamous cell carcinoma, and liver cancer. Over 50% of
human cancer has mutations in the tumor suppressor p53 which regulates cell cycle progression, cell death, senescence, chromosome
integrity, DNA repair, and metastasis. Therefore, understanding of the pathway involved in the regulation of p53 is essential for discovering
novel cancer therapies. With special focus on the tumor suppressor p53 pathway, Dr. Iwakuma dissects the mechanism of cancer
progression using genetically engineered mice, as well as tumor transplantation models, and applies disease models to translational
research, to ultimately cure cancer.

ABSTRACT

Article history: Liver cancer remains one of the most common human cancers with a high mortality rate.
Received: 11-03-2017 Therapies for hepatocellular carcinoma (HCC) remain ineffective, due to the heterogeneity
Accepted: 19-05-2017 of HCC with regard to both the etiology and mutation spectrum, as well as its chemotherapy
Published: 06-06-2017 resistant nature; thus surgical resection and liver transplantation remain the gold standard
of patient care. The most common etiologies of HCC are extrinsic factors. Humans have
Key words: multiple defense mechanisms against extrinsic factor-induced carcinogenesis, of which tumor
Aflatoxin B1, suppressors play crucial roles in preventing normal cells from becoming cancerous. The tumor
vinyl chloride, suppressor p53 is one of the most frequently mutated genes in liver cancer. p53 regulates
iron overload, expression of genes involved in cell cycle progression, cell death, and cellular metabolism
viral infection, to avert tumor development due to carcinogens. This review article mainly summarizes
infection, extrinsic factors that induce liver cancer and potentially have etiological association with
non-alcoholic fatty liver disease p53, including aflatoxin B1, vinyl chloride, non-alcoholic fatty liver disease, iron overload,
and infection of hepatitis viruses.

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