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Cancer Cell. 2004 Jul;6(1):7-10.

Dysregulation of HIF and VEGF is a unifying feature of the familial hamartoma syndromes.

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1
Dana-Farber Cancer Institute and Harvard Medical School, Howard Hughes Medical Institute, 44 Binney Street, Mayer 457, Boston, Massachusetts 02115, USA.

Abstract

The LKB1 tumor suppressor protein controls the activity of the TSC1/TSC2 tumor suppressor complex. Mutations in LKB1 cause Peutz-Jeghers syndrome (PJS), and mutations in either TSC1 or TSC2 cause tuberous sclerosis complex--two syndromes characterized by the development of hamartomas. LKB1 activation by energy deprivation activates AMPK, which in turn phosphorylates and activates TSC2. TSC2 activation results in the inactivation of mTOR, a critical regulator of protein translation. How mTOR dysregulation after inactivation of LKB1 or TSC1/2 contributes to hamartoma development is not known. However, hypoxia-inducible factor (HIF) and VEGF are regulated by mTOR and are likely to play a contributory role.

PMID:
15261137
DOI:
10.1016/j.ccr.2004.06.020
[Indexed for MEDLINE]
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