GOING AWOL: The tumor microenvironment can trigger an intrinsic starvation response that switches melanoma cells from a proliferative to an invasive state, according to work from researchers at Ludwig Oxford. In cell culture, nutrient stress leads to inhibition of translation factor eIF2B, triggering translational and transcriptional suppression of proliferation-associated protein MITF, plus large-scale translational reprogramming. The researchers show that TNFa, a cytokine released by immune cells in the tumor microenvironment, also triggers this pathway, suggesting an explanation for how melanoma cells become invasive in vivo even when food is abundant.© IKUMI KAYAMA/STUDIO KAYAMA
The paper
P. Falletta et al., “Translation reprogramming is an evolutionarily conserved driver of phenotypic plasticity and therapeutic resistance in melanoma,” Genes Dev, 31:18-33, 2017.
In melanoma, tumor cells generally adopt one of two phenotypes: proliferative or invasive. A switch from the first to the second often leads to metastasis and a poorer prognosis. But how this switch gets flipped has been a puzzle for some time—one that Colin Goding, a cancer biologist at Ludwig Oxford in the U.K., has been working on for more than a decade.
A recent clue came from his lab’s discovery that human and mouse melanoma cells are particularly sensitive to glutamine, which is often low in melanoma tumor cores. Supplied with the amino acid, cultured cells ramped up levels ...
