Oncotarget

Research Papers:

LGR5 expression is controled by IKKα in basal cell carcinoma through activating STAT3 signaling pathway

Jiantao Jia, Ying Shi, Bin Yan, Deshen Xiao, Weiwei Lai, Yu Pan, Yiqun Jiang, Ling Chen, Chao Mao, Jian Zhou, Sichuan Xi, Ya Cao, Shuang Liu and Yongguang Tao _

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Oncotarget. 2016; 7:27280-27294. https://doi.org/10.18632/oncotarget.8465

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Abstract

Jiantao Jia1,2,3,*, Ying Shi2,4,5,*, Bin Yan2,4,5,*, Deshen Xiao6, Weiwei Lai2,4,5, Yu Pan6, Yiqun Jiang2,4,5, Ling Chen2,4,5, Chao Mao2,4,5, Jian Zhou7,8, Sichuan Xi9, Ya Cao2,4,5, Shuang Liu1 and Yongguang Tao1,2,4,5

1 Center for Medicine Research, Xiangya Hospital, Central South University, Changsha, Hunan, China

2 Cancer Research Institute, Central South University, Changsha, Hunan, China

3 Pathophysiology Department of Changzhi Medical College, Changzhi, Shanxi, China

4 Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Hunan, China

5 Key Laboratory of Carcinogenesis, Ministry of Health, Hunan, China

6 Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China

7 Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, China

8 Institute of Biomedical Sciences, Fudan University, Shanghai, China

9 Thoracic Surgery Section, Thoracic and GI Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

* These authors have contributted equally to this work

Correspondence to:

Shuang Liu, email:

Yongguang Tao, email:

Keywords: LGR5, IKKα, STAT3, BCC, EGF

Received: July 01, 2015 Accepted: March 16, 2016 Published: March 30, 2016

Abstract

Basal cell carcinomas (BCC) of the skin are the most common of human cancers. The noncanonical NF-κB pathway is dependent on IKKα. However, the role of IKKα in BCC has not been elucidated. We show here that IKKα is expressed in the nucleus in BCC and non-malignant diseases. Nuclear IKKα could directly bind to the promoters of inflammation factors and LGR5, a stem cell marker, in turn, upregulating LGR5 expression through activation of STAT3 signaling pathway during cancer progression. Activation of STAT3 signaling pathway contributes LGR5 expression in dependent of IKKα after the interplay between STAT3 and IKKα. Meanwhile knockdown of IKKα inhibits tumor growth and transition of epithelial stage to mescheme stage. Taken together, we demonstrate that IKKα functions as a bone fide chromatin regulator in BCC, whose promoted expression contributes to oncogenic transformation via promoting expression stemness- and inflammatory- related genes. Our finding reveals a novel viewpoint for how IKKα may involve in BCCs tumor progression in the inflammatory microenvironment.


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