The Maternal Embryonic Leucine Zipper Kinase (MELK) gene is overexpressed in many cancers and has been pursued as a promising therapeutic target in multiple cancer types. But last week researchers from Cold Spring Harbor Laboratory (CSHL) reported in eLife that MELK is not required for cancer growth.
According to Jason Sheltzer, CSHL Fellow, and his colleagues the discrepancy with previous findings results from inherent flaws in the scientific techniques that have been used to link MELK to cancer. "Our study is a good illustration of the self-correcting nature of science," he adds.
Over the past few years, Sheltzer and his team have been performing genomic analyses on tumors surgically removed from cancer patients. The goal has been to identify genes whose activity levels are correlated with low patient survival rates. The researchers then planned to use CRISPR to eliminate the genes from different cancer cell lines one at a time to see if they could kill the cells.
This is where MELK comes in. "Like other labs, we found that MELK tended to be very highly expressed in patients who did not survive very long," Sheltzer says.
Because so many previous studies using a variety of other methods had shown that MELK was essential for cancer cells, Sheltzer believed that his team could use the gene as a positive control in their CRISPR experiments. "We thought we would eliminate MELK and show that it killed cancer cells. Then we could know that our CRISPR techniques were working," Sheltzer says. "But, to our great surprise, the cancer cells didn't die. They just didn't care."
The researchers then performed several experiments to ensure the CRISPR technique was working. "We eventually had to conclude that our technique was fine," Sheltzer says. "Rather, it was the previous findings about MELK's role in cancer that were incorrect."
"We think that this might be a common problem," Sheltzer adds. "There are likely other genes like MELK out there and we're going to use CRISPR to find them."
Image: The growth of human colon cancer cells (raised in culture) is unaffected by the MELK gene. Top row: untreated cells; bottom row: cells treated with a MELK inhibitor drug. Left two columns, control cells; right two columns, cells in which MELK gene has been knocked out. CSHL researchers conclude that MELK is not involved in cancer proliferation. Image courtesy of Sheltzer Lab, CSHL.