CD51 Intracellular Domain Promotes Cancer Cell Neurotropism through Interacting with Transcription Factor NR4A3 in Colorectal Cancer

Tianze Huang; Yanyun Lin; Junguo Chen; Jiancong Hu; Hao Chen; Yanhong Zhang; Bin Zhang; Xiaosheng He

doi:10.3390/cancers15092623

CD51 Intracellular Domain Promotes Cancer Cell Neurotropism through Interacting with Transcription Factor NR4A3 in Colorectal Cancer

Cancers (Basel). 2023 May 5;15(9):2623. doi: 10.3390/cancers15092623.

Authors

Tianze Huang^{1

2}, Yanyun Lin^{1

2}, Junguo Chen^{1

2}, Jiancong Hu², Hao Chen^{1

2}, Yanhong Zhang^{1

2}, Bin Zhang^{1

2}, Xiaosheng He^{1

2}

Affiliations

¹ Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510655, China.
² Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510655, China.

Abstract

The abundant nervous system in intestine provides the basis for perineural invasion (PNI) of colorectal cancer (CRC). PNI is defined as the invasion of the nerves by cancer cells. Although PNI is already known to be an independent prognostic factor in CRC, the molecular mechanism underlying PNI remains obscure. In this study, we first demonstrated that CD51 could promote the neurotropism of tumor cells through cleavage with γ-secretase to generate an intracellular domain (ICD). Mechanistically, ICD of CD51 could bind to the transcription factor NR4A3, and act as a coactivator to promote the expression of downstream effectors, such as NTRK1, NTRK3, and SEMA3E. Pharmacological inhibition of γ-secretase impedes PNI mediated by CD51 in CRC both in vitro and in vivo and may become a potential therapeutic target for PNI in CRC.

Keywords: CD51; colorectal cancer; intracellular domain; perineural invasion.

Abstract

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