4.8 Article Retracted Publication

被撤回的出版物: The RET/PTC-RAS-BRAF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells (Retracted article. See vol. 126, pg. 1603, 2016)

Journal

JOURNAL OF CLINICAL INVESTIGATION
Volume 115, Issue 4, Pages 1068-1081

Publisher

AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI200522758

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In papillary thyroid carcinomas (PTCs), rearrangements of the PET receptor (RET/PTC) and activating mutations in the BRAF or RAS oncogenes are mutually exclusive. Here we show that the 3 proteins function along a linear oncogenic signaling cascade in which RET/PTC induces RAS-dependent BRAF activation and RAS- and BRAF-dependent ERK activation. Adoptive activation of the RET/PTC-RAS-BRAF axis induced cell proliferation and Matrigel invasion of thyroid follicular cells. Gene expression profiling revealed that the 3 oncogenes activate a common transcriptional program in thyroid cells that includes upregulation of the CXCL1 and CXCL10 chemokines, which in turn stimulate proliferation and invasion. Thus, motile and mitogenic properties are intrinsic to transformed thyroid cells and are governed by an epistatic oncogenic signaling cascade.

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