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"By understanding Lkb1 and the mechanisms that control normal skeletal development, we also learn how we might prevent this development from going awry in cancers and other disorders," says Andy McMahon. (Credit: bixentro/Flickr)

bones

Skeleton ‘organizer’ has ties to cancer

Scientists have discovered that a key protein promotes orderly growth and prevents tumors in the skeleton.

In a developing embryo, many bones form based on cartilage templates. The study finds that to form these templates, liver kinase b1 (Lkb1) protein controls the progression of immature, dividing cartilage cells into larger, mature, and fully differentiated cartilage cells.

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Without the protein, the population of immature cartilage cells disproportionately increases, leading to skeletal tumors.

The way that Lkb1 controls the differentiation of cartilage cells is by suppressing what’s known as the “mammalian target of rapamycin (mTOR) pathway”—a very important complex of molecules that coordinates growth in response to available nutrients and other factors.

Problems with the mTOR pathway have been implicated in a host of human diseases, including diabetes, obesity, depression, and many cancers.

The influence of abnormal Lkb1 isn’t restricted to the skeleton, however. Mutant forms of Lkb1 are frequently present in patients with lung, cervical, breast, intestinal, testicular, pancreatic, and skin cancers, and in patients with the Peutz–Jeghers syndrome, characterized by benign polyps in the gastrointestinal tract.

“By understanding Lkb1 and the mechanisms that control normal skeletal development, we also learn how we might prevent this development from going awry in cancers and other disorders,” says Andy McMahon, who directs the University of Southern California Stem Cell initiative and the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research.

Postdoctoral fellow Lick Lai, working in McMahon’s lab, is first author of the paper, which is published in PNAS. Co-authors Brendan N. Lilley and Joshua R. Sanes from Harvard University also contributed to the paper.

National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases provided funding for the work in the McMahon lab, and Lai is a recipient of an Arthritis Foundation Postdoctoral fellowship.

Source: USC

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