p38 mediated ACSL4 phosphorylation drives stress-induced esophageal squamous cell carcinoma growth through Src myristoylation
The comprehension of intricate molecular mechanisms underlying how external stimuli promote malignancy is conducive to cancer early prevention. Esophageal squamous cell carcinoma (ESCC) is considered as an external stimuli (hot foods, tobacco, chemo-compounds) induced cancer, characterized by stepwise progression from hyperplasia, dysplasia, carcinoma in situ and invasive carcinoma. However, the underlying molecular mechanism governing the transition from normal epithelium to neoplastic processes in ESCC under persistent external stimuli has remained elusive. Herein, we show that a positive correlation between p38 and ERK1/2 activation during the progression of ESCC. We identify that phosphorylation of ACSL4 at T679 by p38 enhances its enzymatic activity, resulting in increased production of myristoyl-CoA (C14:0 CoA). This subsequently promotes Src myristoylation and activates downstream ERK signaling. Our results partially elucidate the role of ACSL4 in mediating stress-induced signaling pathways that activate growth cascades and contribute to tumorigenesis.
Authors
- Yan Qiao
- Kangdong Liu (ORCID: https://orcid.org/0000-0002-4425-5625)
- Ziming Dong
- Yaping Guo (ORCID: https://orcid.org/0000-0001-9937-363X)
- Yunshu Shi (ORCID: https://orcid.org/0000-0002-4805-0897)
- Yifei Xie (ORCID: https://orcid.org/0000-0002-8045-0698)
- Chengjuan Zhang (ORCID: https://orcid.org/0000-0002-0702-6890)
- Tong‐Jin Zhao (ORCID: https://orcid.org/0000-0001-6861-3071)
- Jimin Zhao (ORCID: https://orcid.org/0000-0002-3338-9994)
- Zigang Dong (ORCID: https://orcid.org/0000-0002-4174-4028)
- Jing Lü (ORCID: https://orcid.org/0000-0002-9568-0031)
- Xiaoyu Li (ORCID: https://orcid.org/0000-0001-9158-3974)
- Li Peng (ORCID: https://orcid.org/0000-0001-5358-6736)
- Yanan Jiang (ORCID: https://orcid.org/0000-0001-6129-643X)
- Qiang Yuan (ORCID: https://orcid.org/0000-0003-2356-5314)
- Junyong Wang (ORCID: https://orcid.org/0000-0002-7799-4555)
Institutions
- Fudan University (CN)
- Zhengzhou University (CN)
- Henan Tianguan Group (China) (CN)
- China-US (Henan) Hormel Cancer Institute (CN)
- Henan Cancer Hospital (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-04-07
- DOI
- https://doi.org/10.1038/s41467-025-58342-z
- Citations
- 2
- Primary Topic
- Protein Tyrosine Phosphatases
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Henan Province
- Science and Technology Department, Henan Province