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Oncogenic Herpesvirus KSHV Hijacks BMP-Smad1-Id Signaling to Promote Tumorigenesis
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نویسنده
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liang d. ,hu h. ,li s. ,dong j. ,wang x. ,wang y. ,he l. ,he z. ,gao y. ,gao s.-j. ,lan k.
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منبع
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plos pathogens - 2014 - دوره : 10 - شماره : 7
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چکیده
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Kaposi's sarcoma-associated herpesvirus (kshv) is the etiological agent of kaposi's sarcoma (ks),a malignancy commonly found in aids patients. whether ks is a true neoplasm or hyperplasia has been a subject of intensive debate until recently when kshv is unequivocally shown to efficiently infect,immortalize and transform rat primary mesenchymal precursor cells (mm). moreover,kshv-transformed mm cells (kmm) efficiently induce tumors with hallmark features of ks when inoculated into nude mice. here,we showed smad1 as a novel binding protein of kshv latency-associated nuclear antigen (lana). lana interacted with and sustained bmp-activated p-smad1 in the nucleus and enhanced its loading on the id promoters. as a result,ids were significantly up-regulated in kmm cells and abundantly expressed in human ks lesions. strikingly,genetic and chemical inhibition of the bmp-smad1-id pathway blocked the oncogenic phenotype of kshv-transformed cells in vitro and in vivo. these findings illustrate a novel mechanism by which a tumor virus hijacks and converts a developmental pathway into an indispensable oncogenic pathway for tumorigenesis. importantly,our results demonstrate the efficacy of targeting the bmp-smad1-id pathway for inhibiting the growth of kshv-induced tumors,and therefore identify the bmp pathway as a promising therapeutic target for ks. © 2014 liang et al.
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آدرس
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key laboratory of molecular virology and immunology,institut pasteur of shanghai,chinese academy of sciences,shanghai, China, key laboratory of molecular virology and immunology,institut pasteur of shanghai,chinese academy of sciences,shanghai, China, key laboratory of molecular virology and immunology,institut pasteur of shanghai,chinese academy of sciences,shanghai, China, key laboratory of molecular virology and immunology,institut pasteur of shanghai,chinese academy of sciences,shanghai, China, key laboratory of molecular virology and immunology,institut pasteur of shanghai,chinese academy of sciences,shanghai, China, key laboratory of molecular virology and immunology,institut pasteur of shanghai,chinese academy of sciences,shanghai, China, key laboratory of molecular virology and immunology,institut pasteur of shanghai,chinese academy of sciences,shanghai, China, key laboratory of molecular virology and immunology,institut pasteur of shanghai,chinese academy of sciences,shanghai, China, key laboratory of molecular virology and immunology,institut pasteur of shanghai,chinese academy of sciences,shanghai, China, department of molecular microbiology and immunology,keck school of medicine,university of southern california,los angeles,ca, United States, key laboratory of molecular virology and immunology,institut pasteur of shanghai,chinese academy of sciences,shanghai, China
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Authors
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