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Gregory J. Riely, MD, PhD


PPDPF Overexpression: An Avenue for Further Research in Lung Cancer?

By: Celeste L. Dixon
Posted: Monday, May 2, 2022

The high expression of a protein-coding gene called pancreatic progenitor cell differentiation and proliferation factor (PPDPF), a circumstance that has been found in other cancers, has recently been examined in non–small cell lung cancer (NSCLC). Blocking the actions of PPDPF may make NSCLC more receptive to the benefits of radiotherapy, suggesting it also may prove to be a likely therapeutic target, wrote Zhou Chengzhi, PhD, of Guangzhou Medical University, China, and colleagues in the International Journal of Biological Sciences.

Resistance to radiotherapy is a major factor in the poor prognosis of many patients with NSCLC, and overcoming it has been a long-standing challenge, the authors stated. Notably, they found a significant correlation between greater upregulation of PPDPF in NSCLC tissues and cell lines and lower overall survival of these patients.

In their study, which utilized both human and mouse lung cancer cells, the team found that overexpression of PPDPF led to radioresistance in the cells but, conversely, to the knockdown of PPDPF-sensitized lung cancer cells to radiotherapy. Also, they learned, “PPDPF promoted the growth, colony formation, and invasion of lung cancer cells, [but] knockout of PPDPF inhibited tumorigenesis.”

One key to the significance of the work done by Dr. Zhou and co-investigators is their finding that “the expression of PPDPF…inhibits the degradation of BABAM2,” an antiapoptotic protein. The degradation, or destabilization, of BABAM2 seems to boost NSCLC cells’ response to radiation, so when PPDPF has unfettered access to BABAM2, BABAM2 remains stable, “enhancing the resistance of lung cancer cells to radiotherapy.”

PPDPF is also highly expressed in hepatocellular carcinoma, colorectal cancer, and prostate cancer, among other types of cancer, the researchers said. Potentially, further work in targeting this gene’s overexpression may benefit patients with these diseases as well.

Disclosure: The study authors reported no conflicts of interest.

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