Researchers Explain Why Cancer Cells Grow Despite A Lack of Oxygen
In a couple of new researches, experts are reporting on how cancer cells succeed at circumventing the genetic program of growth inhibition.
So far, it was known that PHD proteins (prolyl-hydroxylase domain proteins) play a key role among the regulators of hypoxia by controlling the stability of the hypoxia-induced transcription factors (HIFs) which govern the adaptation of cells to a lack of oxygen. Now researchers have discovered that a special PHD protein, PHD3, also controls the epidermal growth factor receptor (EGFR).
"We have discovered that PHD3 serves as a scaffolding protein, binding to central adapter proteins such as Eps15 and Epsin1 in order to promote the uptake of EGFR into the cells," said lead researcher Professor Amparo Acker-Palmer.
This process is disrupted in tumor cells due to the loss of PHD3. As a result, the internalization of EGFR is suppressed, leading to overactivity of EGFR signals and hence the uncontrolled cell growth.
"Clinically, this discovery is highly relevant, because it shows an alternative mechanism for the hyperactivation of the EGF receptor that is independent of its genetic amplification. It can be therapeutically suppressed by EGFR inhibitors," explained Till Acker, a neuropathologist at the University of Giessen.
"Our work shows an unexpected and new function of PHD3 on the interface of two currently red-hot research areas: Oxygen measurement and EGFR signalling," Acker-Palmer added. "This once again proves how significant growth receptor internalisation is to the development of cancer."
The study was published in the journal Nature Communications.