Research ArticleCancer

Dosage-dependent regulation of VAV2 expression by steroidogenic factor-1 drives adrenocortical carcinoma cell invasion

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Sci. Signal.  07 Mar 2017:
Vol. 10, Issue 469, eaal2464
DOI: 10.1126/scisignal.aal2464

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Target VAV2 for adrenocortical carcinoma

Adrenocortical carcinoma (ACC) is an aggressive cancer of the steroid hormone–producing tissue of the adrenal gland. Patients with ACC have few clinical options and poor prognosis, given that invasion and distant metastasis are often already present at the time of diagnosis. The molecular cause is unknown, but various genes exhibit increased expression in ACC tumors, including the gene encoding the transcription factor SF-1. Ruggiero et al. found that the expression of an SF-1 target gene encoding guanine exchange factor VAV2 was a critical mediator of changes in ACC cell morphology that enabled invasion in both culture and in vivo models. VAV2 is associated with progression in other tumor types, and pharmacological inhibitors against VAV2 are under development. The findings suggest that targeting VAV2 may be a future clinical option for ACC patients.