Noncanonical IL6 Signaling-Mediated Activation of YAP Regulates Cell Migration and Invasion in Ovarian Clear Cell Cancer
Walid J Azar, Elizabeth L Christie, Chris Mitchell, David S Liu, George Au-Yeung, David DL Bowtell
CANCER RESEARCH | AMER ASSOC CANCER RESEARCH | Published : 2020
Ovarian clear cell adenocarcinoma (OCCA) is characterized by a particularly poor response to conventional chemotherapy and a short overall survival time in women with established disease. The development of targeted treatments for OCCA relies on a better understanding of its molecular characteristics. IL6 is strongly expressed in OCCA and may therefore provide a novel therapeutic target. Here we use CRISPR/Cas9 and conditional short hairpin interfering RNA to perform loss-of-function studies in human OCCA cell lines to explore the requirement for IL6 in vitro and in vivo. While reduction of IL6 expression exerted limited effects in vitro, its attenuation significantly impaired tumor growth a..View full abstract
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Awarded by National Health and Medical Research Council of Australia (NHMRC)
Awarded by U.S. Army Medical Research and Materiel Command
This work was supported by the National Health and Medical Research Council of Australia (NHMRC APP1044447, APP1117044, and APP631701). The Australian Ovarian Cancer Study was supported by the U.S. Army Medical Research and Materiel Command under DAMD17-01-1-0729, The Cancer Council Victoria, Queensland Cancer Fund, The Cancer Council New South Wales, The Cancer Council South Australia, The Cancer Foundation of Western Australia, The Cancer Council Tasmania and the National Health and Medical Research Council of Australia (NHMRC; ID400413, ID400281). The AOCS gratefully acknowledges additional support from Ovarian Cancer Australia and the Peter MacCallum Cancer Centre Foundation. We gratefully acknowledge additional support from Mrs. Margaret Rose AM and the Rose family, The WeirAnderson Foundation, Border Ovarian Cancer Awareness Group, Wendy Taylor and Arthur Coombs and family. E. Christie was supported by the Victorian Cancer Agency and the National Health and Medical Research Council of Australia.