Publication Highlight: Liver Cancer Initiation Requires p53 Inhibition by CD44-Enhanced Growth Factor Signaling

Posted on August 1, 2018 by MFeiock


Researchers Pinpoint Molecule Fueling Liver Cancer Development

Study explains how carcinogens turn liver cells into cancer cells

New research from our UCSD Superfund Research Center explains how liver cells with DNA damage manage to survive and divide, fueling liver cancer. The study highlights the importance of a family of molecules called CD44 proteins, which are located on the surface of cells. UCSD investigators found that CD44 allows cells to override the body’s natural protective response to DNA damage. The results suggest mutiple potential targets for tumor prevention and treatment in the liver, as wells as other organs. 

A tumor suppressor protein called p53 is normally activated when DNA damage occurs. p53 stops the cell from dividing, triggers cell death, and prevents mutations caused by DNA damage from spreading. Without this protective response, damaged cells continue to divide, accumulating mutations and leading to cancer. To understand the underlying mechanism of this process, the researchers looked at liver cells in mice, as well as samples from humans.

To read more about this research, please visit the study which is published online in Cancer Cell  (June 11, 2018) and also showcased by our funding agency, NIEHS, as a "Paper of the Month" in Environmental Factor (August 2018) and as a Superfund Research Program, Research Brief # 284 

PDF version of NIEHS Research Brief 284 (August 1, 2018)]

Hepatocellular carcinoma (HCC) most commonly occurs in people with liver disease, particularly in people with chronic hepatitis B and C. Symptoms often don't appear in the early stages of the cancer. Later, symptoms include weight loss, upper abdominal pain, or yellowing of the skin (jaundice). Treatments may include surgery, transplant, freezing or heating the cancer cells, and chemotherapy.

Published study:

Dhar D, Antonucci L, Nakagawa H, Kim JY, Glitzner E, Caruso S, Shalapour S, Yang L, Valasek MA, Lee S, Minnich K, Seki E, Tuckermann J, Sibilia M, Zucman-Rossi J, Karin M. (2018) Liver cancer initiation requires p53 inhibition by CD44-enhanced growth factor signaling. Cancer Cell 33(6):1061–1077. 
doi: 10.1016/j.ccell.2018.05.003 |  PMID: 29894692  PMCID:

For more information, please visit the following UCSD Superfund Research Project:

UCSD Superfund Research Center - Project 1: Dr. Michael Karin

Michael Karin, Ph.D.
University of California, San Diego
Department of Pharmacology
La Jolla, California 92093-0723

Main Image Credit:
Hepatocellular carcinoma intermed mag.jpg. (2017, November 11)
Wikimedia Commons, the free media repository.



UCSD Superfund Research Center
University of California, San Diego
Pharmacology Department
9500 Gilman Drive, Mail Code 0722
La Jolla, CA 92093-0722