HOXC8 Promotes Growth and Migration of Breast Cancer Cells by Activating GDF15 Transcription
SHI Jialu#, XU Shanshan#, CHEN Rong, CHEN Qian, LI Yong*
HOX (homeobox) gene family consists of homeodomain-containing transcription factors and their dysregulation is related to development of various cancers. Previously, it had been reported that HOXC8 which was a member of HOX gene family, promoted migration and metastasis of breast cancer cells. HOXC8 expression was found by RNA-seq, Western blot and RT-PCR analyses to result in up-regulation of GDF15 (growth and differentiation factor 15) in breast cancer cells. HOXC8 was demonstrated by chromatin immunoprecipitation and luciferase assays to bind to the promoter of GDF15. As transcription factor, it was to activate GDF15 expression. Moreover, GDF15 expression promoted cell viability, anchorage-independent growth, migration and the formation of filopodium/lamellipodium of breast cancer cells. It was further demonstrated that HOXC8 promoted cell growth and migration by inducing GDF15 expression in breast cancer cells. Additionally, HOXC8 or GDF15 gene was amplified in invasive breast cancer and up-regulation of HOXC8 or GDF15 was statistically associated with poor prognosis of breast cancer patients. Altogether, this study showed that HOXC8-GDF15 axis played an important role in breast cancer progression and might present a promising target for breast cancer treatment.
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