FAM83D associates with high tumor recurrence after liver transplantation involving expansion of CD44+ carcinoma stem cells
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Binyi Lin1,2,3, Tianchi Chen1,2, Qijun Zhang1,2, Xiaoxiao Lu1,2, Zhiyun Zheng1,2, Jun Ding1,2, Jinfeng Liu1,2, Zhe Yang1,2,3, Lei Geng1,2,3, Liming Wu1,2,3, Lin Zhou1,2,3, Shusen Zheng1,2,3
1Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou 310003, China
2Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
3Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China
Shusen Zheng, email: firstname.lastname@example.org
Lin Zhou, email: email@example.com
Keywords: FAM83D, carcinoma stem cells, hepatocellular carcinoma, liver transplantation, CD44
Received: April 05, 2016 Accepted: October 01, 2016 Published: October 18, 2016
To investigate the potential oncogene promoting recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT), throughput RNA sequencing was performed in a subgroup of HCC patients. The up-regulated FAM83D in HCC tissues was found and further verified in 150 patients by real-time PCR and immunohistochemistry. FAM83D overexpression significantly correlated with high HCC recurrence rate following LT and poor HCC characteristics such as high AFP, poor differentiation. Of cancer stem cells (CSCs) markers, CD44 expression was effectively suppressed when FAM83D was knocked down by siRNA. Meanwhile, the siRNA transfected cells suppressed formation of sphere and ability of self-renew. In a xenograft tumorigenesis model, FAM83D knockdown apparently inhibited tumor growth and metastasis. Microarray assays revealed that FAM83D promotes CD44 expression via activating the MAPK, TGF-β and Hippo signaling pathways. Furthermore, CD44 knockdown presented reverse effect on above signaling pathways, which suggested that FAM83D was a key activator of loop between CD44 and above signaling pathways. In conclusion, FAM83D promotes HCC recurrence by promoting CD44 expression and CD44+ CSCs malignancy. FAM83D provides a novel therapeutic approach against HCC recurrence after LT.
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