Oxygen Deprivation May Prompt Breast Cancer to Migrate Elsewhere in Body

Oxygen Deprivation May Prompt Breast Cancer to Migrate Elsewhere in Body

Oxygen deprivation can activate a cell mechanism that prompts triple-negative breast cancer cells to migrate to other parts of the body, a finding that could lead to better treatments, a study says.

The research, “HIFI-α Activation Underlies A Functional Switch In The Paradoxical Role Of Ezh2/PRC2 In Breast Cancer,” was published in the journal Proceedings of the National Academy of Sciences.

Several genes can either help suppress cancer growth or promote tumor cells’ survival and migration, depending on what’s happening in the cells’ environment.

Although researchers have known that the PRC2 and EZH2 genes can suppress or promote cancer cells, they didn’t know what prompted the genes to take one path or the other.

“Different cancers are driven by different mechanisms, and some signaling components, such as the EZH2/PRC2 complex, can be both tumor-suppressive and tumor-promoting,” Qiang Yu, who headed the research team, said in a news release. Learning why the genes suppress cancer in some instances and promote it in others may lead to better therapies, he added.

Previous findings have shown that the genes’ impact differs by breast cancer subtype, suggesting they are not always working together.

As an example, there are high amounts of EZH2 in triple-negative breast cancer but low amounts of PRC2.

Researchers discovered that oxygen deprivation, or hypoxia, triggered a drop in PRC2 expression activity — the process by which PRC2 translates encoded gene information to other cell parts. The reduced PRC2 activity allowed EZH2 to partner with another protein, FoxM1.

Importantly, the EZH2/FoxM1 amalgam promoted the expression of genes that help cancer cells migrate, worsening the condition of women with triple-negative breast cancer.

When oxygen levels are normal, PRC2 suppresses the expression of genes that participate in cancer migration, the researchers found. But when oxygen levels drop, EZH2 teams up with FoxM1 to activate signaling pathways leading to less chance of survival.

The same dynamics may lead to problems regulating other cancer types when EZH2 is present, Yu said.

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