Research ArticleCholesterol Metabolism

Neuregulin-activated ERBB4 induces the SREBP-2 cholesterol biosynthetic pathway and increases low-density lipoprotein uptake

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Science Signaling  03 Nov 2015:
Vol. 8, Issue 401, pp. ra111
DOI: 10.1126/scisignal.aac5124

Providing cholesterol for proliferation

Although cholesterol has received a lot of bad press, this lipid molecule is actually an essential component of cellular membranes. Growing or dividing cells need more cholesterol than quiescent cells. The activity of epidermal growth factor receptor (EGFR) family members stimulates cell proliferation in physiological and pathophysiological contexts, such as cancer. Haskins et al. found that neuregulin 1 (NRG1)–mediated activation of the EGFR member ERBB4 stimulated the transcription factor SREBP-2, which enhanced the expression of the receptor needed to uptake cholesterol-rich low-density lipoproteins and genes involved in cholesterol biosynthesis in cultured breast epithelial cells. Pharmacological inhibition of EGFR activity or SREBP-2 activity suppressed the NRG1-mediated induction of cholesterol synthesis–related genes. Thus, EGFR signaling alters cellular lipid metabolism, enabling cells to acquire or synthesize molecules necessary for proliferation.

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