by Cristy Lytal
This is a mouse femur with an enchondroma-like structure. Credit: Lick Lai
Most people think that their planners or their iPhones keep them organized, when proteins such as liver kinase b1 (Lkb1) actually have a lot more to do with it. New research from postdoctoral fellow Lick Lai in the lab of USC scientist Andy McMahon published in Proceedings of the National Academy of Sciences (PNAS) sheds light on how this important protein keeps people organized on a basic level by promoting orderly skeletal growth and preventing skeletal tumors.
In a developing embryo, many bones form based on cartilage templates. The study found that to form these templates, Lkb1 protein controls the progression of immature, dividing cartilage cells into larger, mature and fully differentiated cartilage cells. Without Lkb1, 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," said McMahon, who directs the USC Stem Cell initiative and the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC.
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© Medical Xpress 2011-2013, Phys.org network
by Cristy Lytal
This is a mouse femur with an enchondroma-like structure. Credit: Lick Lai
Most people think that their planners or their iPhones keep them organized, when proteins such as liver kinase b1 (Lkb1) actually have a lot more to do with it. New research from postdoctoral fellow Lick Lai in the lab of USC scientist Andy McMahon published in Proceedings of the National Academy of Sciences (PNAS) sheds light on how this important protein keeps people organized on a basic level by promoting orderly skeletal growth and preventing skeletal tumors.
In a developing embryo, many bones form based on cartilage templates. The study found that to form these templates, Lkb1 protein controls the progression of immature, dividing cartilage cells into larger, mature and fully differentiated cartilage cells. Without Lkb1, 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," said McMahon, who directs the USC Stem Cell initiative and the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC.
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More information: www.pnas.org/content/early/2013/11/07/1309001110.abstract
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Research led by Dr. Suresh Alahari, Professor of Biochemistry and Molecular Biology at LSU Health Sciences Center New Orleans, is the first to report that two specific tumor suppressor genes work in concert to inhibit the ...
Oncogene inhibits tumor suppressor to promote cancer: Study links B-RAF and LKB1
Jan 29, 2009
Scientists have uncovered an interesting connection between two important protein kinase signaling pathways that are associated with cancer. The research, published by Cell Press in the January 30th issue of the journal Molecular Ce ...
Hungry cells
Jun 16, 2009
People who suffer from Peutz-Jeghers syndrome, a rare inherited cancer syndrome, develop gastrointestinal polyps and are predisposed to colon cancer and other tumor types. Carefully tracing the cellular chain-of-command ...
Gene inactivation drives spread of melanoma: study
Jun 11, 2012
Why do some cancers spread rapidly to other organs and others don't metastasize? A team of UNC researchers led by Norman Sharpless, MD, have identified a key genetic switch that determines whether melanoma, a lethal skin ...
Scientists discover key signaling pathway that makes young neurons connect
Jun 20, 2013
Neuroscientists at The Scripps Research Institute (TSRI) have filled in a significant gap in the scientific understanding of how neurons mature, pointing to a better understanding of some developmental brain disorders.
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Deadly brain illness discovered in British family
15 hours ago
(HealthDay)—A British family harbors a deadly inherited illness that destroys the brain in a way that is similar to the dreaded mad cow disease, researchers report.
Gut microbes in healthy kids carry antibiotic resistance genes
16 hours ago
Friendly microbes in the intestinal tracts (guts) of healthy American children have numerous antibiotic resistance genes, according to results of a pilot study by scientists at Washington University School of Medicine in ...
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19 hours ago
Researchers at the Cardiovascular Research Center at Icahn School of Medicine at Mount Sinai have successfully tested a powerful gene therapy, delivered directly into the heart, to reverse heart failure in ...
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