Wistar Scientists Unveil Mechanism That Stops Cancer Progression by Interfering With Cancer Cell Metabolism
During progression from a precancerous lesion to an aggressive tumor and then metastasis, cancer cells rewire their metabolism to support increased energy demands due to continuous growth and adapt to unfavorable conditions in the surrounding environment.
In a study published in the journal Science Advances, Dr. Altieri and colleagues discovered a new mechanism that suppresses tumor development by interfering with metabolism and with the function of mitochondria, the cell’s powerhouse.
The team studied a gene called Parkin that is known for its protective function in brain cells and is altered in Parkinson’s disease. Previous evidence indicated that Parkin might have a role in regulating cancer cell metabolism and suppressing tumor growth, but the mechanism remained elusive.
The team found that Parkin expression was low or undetectable in tumors compared with their respective normal counterpart.
When they re-introduced Parkin in prostate cancer cells and other cancer cell types that did not express the protein, they observed reduced cell movement and a blocking of invasion, while deletion of Parkin in normal cells increased cell motility.
In vivo, Parkin-expressing prostate cancer cells formed smaller tumors and had lower metastatic potential.
Role of Parkin and Mitochondria
The Altieri lab has contributed important knowledge in the role mitochondria play in cancer, showing that changes in their size, shape and distribution within cells increase their ability to move and invade other tissues and acquire other aggressive traits.
In the new study, they discovered that Parkin interferes with the function of mitochondria in cancer cells, and, as a consequence, blocks tumor cell motility, which is critical for their ability to disseminate and invade other tissues during metastasis.
Forced Parkin expression in cancer cells also resulted in reduced energy production.
In addition, researchers found that exposing Parkin-expressing cancer cells to stress conditions such as nutrient deprivation and DNA-damaging agents resulted in a strong increase in Parkin levels.
From this study, Parkin emerges as a critical, stress-activated effector of a tumor suppression pathway that stops cancer progression and metastasis by interfering with the ability of cancer cells to reprogram their metabolism.