Researchers in Canada and the US have found a protein that appears to help cancer develop by playing a key role in cell growth and proliferation; they said the discovery helps us better understand cancer physiology and opens the door to new cancer therapies, including diagnostic tools and personalized treatments.

These are the findings of a study published online before print on 11 December in the Proceedings of the National Academy of Sciences (PNAS). The first author is Dr Armen Parsyan, a post-doctoral fellow in the Department of Biochemistry and Rosalind Morris Goodman Cancer Centre in the Faculty of Medicine at McGill University in Montreal in Quebec.

Cell growth and tumor growth rely on protein synthesis: a process where chains of amino acids are assembled according to the instruction manual in the genetic code. Before the amino acid chain can be assembled, the genetic code is first “translated” onto a specific polypeptide “template” using messenger RNA (mRNA).

For the study, Parsyan and colleagues investigated DHX29, a helicase protein that is necessary for translation initiation, and which has recently been described by co-author Dr Tatyana Pestova’s laboratory at SUNY Downstate Medical Center in New York.

This study builds on Pestova’s work, by documenting the role of DHX29 in protein synthesis and cancer development.

The researchers found that depleting DHX29 from living cells led to a significant decrease of cancer cell proliferation.

Lack of DHX29 appeared to impede cancer growth both in cultured cells and in xenografts (living tissue grafted onto laboratory animals): the tumors formed were much smaller than usual.

Parsyan told the press they were surprised to find yet another translation initiation factor playing a key role in cancer cell proliferation:

“This is another clear indication of the key role that translation initiation factors play in the etiology and pathogenesis of cancer. It’s clear we’re on the right direction and must continue on this avenue of research.”

Lead author Dr Nahum Sonenberg, who last year won the Gairdner Prize for his discoveries in the areas of protein synthesis in human cells, said:

“Two decades ago we reported the first translation initiation factor that promotes tumorigenesis.”

“Since then several other translation initiation factors were documented to cause cancer, but it’s still exciting to find novel initiation factors that add to our knowledge of cancer development,” added Sonnenberg, who has also been named Researcher of the Year for Biomedical and Clinical Research by the Canadian Institutes of Health Research.

The authors wrote that:

“Down-regulation of DHX29 leads to impaired translation”, and that “DHX29 depletion also impedes cancer cell growth in culture and in xenografts”.

They concluded that:

“Thus, DHX29 is a bona fide translation initiation factor that potentially can be exploited as a target to inhibit cancer cell growth.”

“The helicase protein DHX29 promotes translation initiation, cell proliferation, and tumorigenesis.”

Armen Parsyan, David Shahbazian, Yvan Martineau, Emmanuel Petroulakis, Tommy Alain, Ola Larsson, Geraldine Mathonnet, Gritta Tettweiler, Christopher U. Hellen, Tatyana V. Pestova, Yuri V. Svitkin and Nahum Sonenberg.

PNAS published online before print December 11, 2009.

DOI:10.1073/pnas.0909773106

Source:McGill University.

Written by: Catharine Paddock, PhD