Researchers have discovered that mitophagy – the selective degradation of damaged mitochondria – allows liver cancer stem cells to survive and contribute to liver tumor growth. Their findings suggest that halting mitophagy temporarily is a potential new therapeutic target for liver cancer.
The study “Mitophagy Controls the Activities of Tumor Suppressor p53 to Regulate Hepatic Cancer Stem Cells” was published in the journal Molecular Cell.
Liver cancer has been on the rise, with the Centers for Disease Control and Prevention pointing to an increase in new cases of up to 38 percent in nine years – from 2003 to 2012 – that resulted in 23,000 deaths (a 56 percent bump).
The cancer mortality is linked to its ability to resist the majority of chemotherapy drugs – only three drugs have been capable of shrinking liver tumors, but the cancer develops resistance fast and eventually overcomes the therapy.
The discovery that mitophagy may present a therapeutic target for liver cancer was made by researchers at the Keck School of Medicine of USC. They found that mitophagy benefits hepatic cancer stem cells, allowing tumors to proliferate.
This happens because a key tumor suppressor protein – called p53 – binds to mitochondria before traveling to the cell nucleus to activate a series of genes that stop cells’ malignant transformation.
If a lot of mitochondria are removed, then cells lose the tumor suppressor p53, allowing hepatic cancer stem cells to proliferate and the tumor to grow.
“Liver cancer is difficult to treat, and most patients who are diagnosed with it will die within a five-year period,” Jing-Hsiung James Ou, study lead author and a professor of molecular microbiology and immunology at the Keck School of Medicine, said in a press release. “My team has identified how liver cancer stem cells are maintained. Without these ‘seeds of cancer,’ liver tumors would shrink and eventually disappear.”
Inhibiting mitophagy temporarily, researchers found, reduced the number of hepatic cancer stem cells. Because these cells fuel tumor growth, reducing their number leads to tumor shrinkage and eventual disappearance.
“Now that we understand the molecular process, we will be able to target this pathway to stop the production of cancer stem cells,” Ou said. “If cancer stem cells are gone, cancer is gone.”