Mitochondrial Inhibition May Block Malignant Tumor Growth

Mitochondrial Inhibition May Block Malignant Tumor Growth

A study recently published in the journal Cell Reports revealed the mechanism by which a benign kidney tumor can develop into an aggressive cancer, and the role mitochondria dysfunction has on this process. The study, titled “The Genomic Landscape of Renal Oncocytoma Identifies a Metabolic Barrier to Tumorigenesis,” was led by researchers at Rutgers Cancer Institute of New Jersey (CINJ).

Oncocytomas are tumors in epithelial cells with an excessive amount of mitochondria (oncocyte cells). These tumors are usually benign but can become malignant. Oncocytomas are characterized by pathogenic mitochondrial mutations and the accumulation of respiration-defective mitochondria, and can develop in several tissues and organs, including the kidney (renal oncocytoma).

Researchers identified two main subtypes of renal oncocytoma: Type 1 which is diploid (a paired number of chromosomes), and Type 2 that is aneuploid (an abnormal number of chromosomes) due to recurrent loss of certain chromosomes.

The study’s co-senior authors, Dr. Chang S. Chan, assistant professor of medicine at Rutgers Robert Wood Johnson Medical School, and Dr. Eileen White, professor of molecular biology and biochemistry and Rutgers Cancer Institute Associate Director for Basic Science, together with the study’s co-lead author Dr. Shilpy Joshi, shared information about their findings in a Rutgers’ news release.

According to the release, the team’s goal was to “identify what limits some tumors to benign disease. To this end we sequenced 11 benign human renal oncocytoma samples. … The samples were characterized based on chromosome loss. ‘Type 1’ was designated as having no chromosome loss, while ‘Type 2’ samples were designated as having specific chromosome loss.”

Researchers found that Type 2 renal oncocytoma can progress into a more aggressive form of malignant kidney cancer known as eosinophilic chromophobe renal cell carcinoma (ChRCC). In contrast, Type 1 oncocytoma was not found to progress to malignant disease. “These findings suggest that determining the subtype of oncocytoma is important, and patients with Type 2 should be followed more closely,” the team said.

Both types of oncocytomas exhibited a defective mitochondrial function, “oncocytomas showed genetic defects in the production of energy, due to mutations in the mitochondrial genome. Mitochondria are the powerhouses of the cell and mutations that inactivate their function in these oncocytomas result in insufficient energy levels to support tumor progression, which explains their benign nature,” explained the authors. “This reveals a novel tumor-suppressive mechanism and suggests that mitochondrial inhibitors like the diabetes drug metformin, which is currently being tested in the treatment of some cancers, may work this way. A breach of this barrier in Type 2 samples by a common mutation known as p53 may allow the benign tumor to progress to eosinophilic ChRCC.”

Mutations in the tumor suppressor gene p53 have been linked to the development of several cancers, as they usually result in a promotion of tumor growth. Now researchers reported that p53 mutation may enable progression to eosinophilic ChRCC.

When asked about the relevance of their findings, the authors commented, “Benign tumors are localized and can be treated by removing from the body unlike malignant tumors that are aggressive and tend to spread in other parts of the body and can represent a lethal form of disease. Mechanisms that restrict tumors to benign disease can inform approaches to cancer therapy. This also suggests that inhibiting mitochondria with metformin may have anti-cancer activity in many different cancers.”

The research team concluded that an impaired mitochondrial function seems, in this case, to act as a barrier to malignant tumorigenesis.

Leave a Comment

Your email address will not be published. Required fields are marked *