OXTRHigh stroma fibroblasts control the invasion pattern of oral squamous cell carcinoma via ERK5 signaling

Liang Ding, Yong Fu, Nisha Zhu, Mengxiang Zhao, Zhuang Ding, Xiaoxin Zhang, Yuxian Song, Yue Jing, Qian Zhang, Sheng Chen, Xiaofeng Huang, Lorraine A O’Reilly, John Silke, Qingang Hu () and Yanhong Ni ()
Additional contact information
Liang Ding: Medical School of Nanjing University
Yong Fu: Medical School of Nanjing University
Nisha Zhu: Medical School of Nanjing University
Mengxiang Zhao: Medical School of Nanjing University
Zhuang Ding: Medical School of Nanjing University
Xiaoxin Zhang: Medical School of Nanjing University
Yuxian Song: Medical School of Nanjing University
Yue Jing: Medical School of Nanjing University
Qian Zhang: Medical School of Nanjing University
Sheng Chen: Medical School of Nanjing University
Xiaofeng Huang: Medical School of Nanjing University
Lorraine A O’Reilly: The Walter and Eliza Hall Institute of Medical Research
John Silke: The Walter and Eliza Hall Institute of Medical Research
Qingang Hu: Medical School of Nanjing University
Yanhong Ni: Medical School of Nanjing University

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: Abstract The Pattern Of Invasion (POI) of tumor cells into adjacent normal tissues clinically predicts postoperative tumor metastasis/recurrence of early oral squamous cell carcinoma (OSCC), but the mechanisms underlying the development of these subtypes remain unclear. Focusing on the highest score of POIs (Worst POI, WPOI) present within each tumor, we observe a disease progression-driven shift of WPOI towards the high-risk type 4/5, associated with a mesenchymal phenotype in advanced OSCC. WPOI 4-5-derived cancer-associated fibroblasts (CAFsWPOI4-5), characterized by high oxytocin receptor expression (OXTRHigh), contribute to local-regional metastasis. OXTRHigh CAFs induce a desmoplastic stroma and CCL26 is required for the invasive phenotype of CCR3+ tumors. Mechanistically, OXTR activates nuclear ERK5 transcription signaling via Gαq and CDC37 to maintain high levels of OXTR and CCL26. ERK5 ablation reprograms the pro-invasive phenotype of OXTRHigh CAFs. Therefore, targeting ERK5 signaling in OXTRHigh CAFs is a potential therapeutic strategy for OSCC patients with WPOI 4-5.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-32787-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32787-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-32787-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().