2. Academic Validation
  3. Dedifferentiated Schwann cells promote perineural invasion mediated by the PACAP paracrine signalling in cervical cancer

Dedifferentiated Schwann cells promote perineural invasion mediated by the PACAP paracrine signalling in cervical cancer

  • J Cell Mol Med. 2023 Oct 13. doi: 10.1111/jcmm.17897.
Guoqiang Chen 1 2,  Zhen Zheng 3,  Hao Sun 1,  Jiahao You 1,  Jing Chu 1,  Jinghai Gao 1,  Lei Qiu 4,  Xiaojun Liu 1
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Second Affiliated Hospital of Naval Medical University, Shanghai, China.
  • 2 Department of Gynecology, The People's Hospital of Baoan Shenzhen, The Second Affiliated Hospital of Shenzhen University, Shenzhen, China.
  • 3 Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 4 School of Pharmacy, Naval Medical University, Shanghai, China.
PMID: 37830980 DOI: 10.1111/jcmm.17897
Abstract

Perineural invasion (PNI) has emerged as a key pathological feature and be considered as a poor prognostic factor in cervical Cancer. However, the underlying molecular mechanisms are largely unknown. Here, PNI status of 269 cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) samples were quantified by using whole-slide diagnostic images obtained from The Cancer Genome Atlas. Integrated analyses revealed that PNI was an indicative marker of poorer disease-free survival for CESC patients. Among the differentially expressed genes, ADCYAP1 were identified. Clinical specimens supported that high expression of PACAP (encoded by ADCYAP1) contributed to PNI in CESC. Mechanistically, PACAP, secreted from cervical Cancer cells, reversed myelin differentiation of Schwann cells (SCs). Then, dedifferentiated SCs promoted PNI by producing chemokine FGF17 and by degrading extracellular matrix through secretion of Cathepsin S and MMP-12. In conclusion, this study identified PACAP was associated with PNI in cervical Cancer and suggested that tumour-derived PACAP reversed myelin differentiation of SCs to aid PNI.

Keywords

Schwann cells; cervical cancer; dedifferentiated; perineural invasion; pituitary adenylate cyclase-activating polypeptide.

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