Master protein for tumor growth

Written byAndrea Gawrylewski

| 2 min read

Researchers have identified a master protein that regulates some 1,000 genes controlling for tumor growth and metastasis in breast cancer, according to a linkurl:paper;http://www.nature.com/nature/journal/v452/n7184/abs/nature06781.html published today in Nature. The researchers, led by linkurl:Terumi Kohwi-Shigematsu;http://www.lbl.gov/lifesciences/labs/kohwi-shigematsu_lab.html at Lawrence Berkeley National Laboratory, stumbled upon SATB1's heightened expression while screening aggressive human breast cancer tumor samples. Surprisingly, they found that SATB1 is only expressed in aggressive tumors. "SATB1 is a gene organizer, a regulator of a large body of genes," Kohwi-Shigematsu told The Scientist. "Almost 1,000 genes changed expression with SATB1 expressed." The SATB1 protein linkurl:regulates chromatin structure;http://www.the-scientist.com/article/display/20767/ and tissue architecture -- properties essential for tumor cells to transition into metastatic states. In addition , SATB1 regulates genes that come from all different sorts of molecular pathways, from signaling genes to growth factors. But they are all "in favor" of linkurl:metastasis;http://www.the-scientist.com/news/home/53583/ and downregulate tumor suppressor genes. "One could argue that SATB1 is yet another foot soldier in the transcription arsenal of master regulators that could be modifying the transition programming that drives metastasis," Valerie Weaver, from the Unviersity of California, San Francisco, who was not involved in the study, told The Scientist. "But this one is unique in that it is actually linked to nuclear cell and tissue architecture, and therefore could be an exciting candidate to follow up on" as a regulator of tumor behavior. Previous work has linked SATB1 to T cell activation in adaptive immunity. But there is debate over the importance of this new finding. SATB1 shares common properties with some half a dozen other transcription factor linkurl:genes;http://www.the-scientist.com/news/home/53062/ that have been associated with metastasis, linkurl:Robert Weinberg,;http://www.wi.mit.edu/research/faculty/weinberg.html from the Whitehead Institute, told The Scientist in an Email. "It hardly forges a new conceptual paradigm, since it does almost precisely (if not precisely) what a number of these other 'master control genes' do, including Snail, Slug, Twist, SIP1, Goosecoid, etc, etc." Kohwi-Shigematsu's group has found that high expression of SATB1 correlates with breast cancer patient survival rate, leading them to predict that SATB1 may be an important clinical prognostic tool in the future. But since SATB1 is also involved in T cell activation, the researchers are currently trying to develop a nanocapsule that can deliver an SATB1 inhibitor directly into breast cancer tumor cells only. In two other studies also published in Nature today, a group led by linkurl:Lewis Cantley,;http://sysbio.med.harvard.edu/faculty/cantley/ at Harvard Medical School, reports targeting the linkurl:tumor cell energy pathway;http://www.the-scientist.com/2007/12/1/44/1/ in order to curb tumor growth. Previous studies have shown that tumor cells need the enzyme pyruvate kinase -- known as M2 -- in the metabolic cycle of tumorigenesis. In the first paper, the researchers used a short hairpin RNA to knockdown M2 expression and replace it with an isoform of the enzyme called M1 in colon cancer samples. They observed that this switch curbed tumor cell growth, even in mice xenografts. In the accompanying paper, Cantley's group demonstrated that M2 binds peptides that control tumor growth-related energy metabolism, expanding on M2's mechanism of action in tumor cell metabolism. Certainly tumor cell metabolism is implicit in tumor growth and metastasis, all of which is linked closely to the tumor microenvironment, Weaver said. There is evidence that genes that regulate tissue modification can also regulate metabolism genes, she added, suggesting that a link likely exists between master regulators like SATB1 and tumor cell cycle. "The key point is fleshing out the details -- figuring out what the molecular players are and whether or not there is a hierarchy in this. And there will be."

Master protein for tumor growth

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