Recurrence is the main cause of death after tumor treatment. Tumor cells remain inactive and are activated again with more aggressively. This phenomenon has been one of the biggest mystery of tumor. Researchers from University of California San Francisco have identified the key protein HIGD1A in this process. The study was published in Cell Reports.

Hypoxia inducible factor(HIF-1) is a widely expressed transcription factor that regulates the survival of cells during oxygen and glucose deprivation. HIF can also regulate tumor metabolism by repressing respiration while promoting glycolysis, which enables rapid tumor cell proliferation.

It has been confirmed that some of the most metabolically compromised tumor regions found around their necrotic cores fail to induce HIF activity, potentially due to glucose starvation. Interestingly, these regions still express the HIF-1 target HIGD1A.

In this study, scientists found that HIGD1A interacts with the mitochondrial electron transport chain, modulates oxygen consumption, ROS production, and AMPK activity to promote cell survival during glucose starvation, while simultaneously suppressing tumor growth invivo. Their studies confirm these observations and identify HIGD1A as an important upstream component of this signaling cascade. Furthermore , HIGD1A repression is associated with tumor recurrence in breast cancers following therapy, consistent with their observations that HIGD1A expression helps repress tumor growth.

These findings therefore provide novel insights into tumor cell adaptation mechanisms to extreme environments and suggest that HIGD1A may play an important role in tumor dormancy or recurrence mechanisms.

Reference:

 Ameri K, Jahangiri A, Rajah A M, et al. HIGD1A Regulates Oxygen Consumption, ROS Production, and AMPK Activity during Glucose Deprivation to Modulate Cell Survival and Tumor Growth[J]. Cell reports, 2015, 10(6): 891-899