Research Paper|Volume 13, Issue 7|pp 10312—10325

Membrane-cytoplasm translocation of annexin A4 is involved in the metastasis of colorectal carcinoma

Ya Peng¹, Zhaoyu Zhang^2,³, Ailing Zhang¹, Changhong Liu², Yingnan Sun³, Zixuan Peng², Yang Liu²

¹Hunan Provincial People's Hospital and the Affiliated Hunan Normal University, Changsha 410081, Hunan, China
²The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha 410008, Hunan, China
³Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha 410013, Hunan, China

* Equal contribution

Received: December 3, 2019Accepted: October 27, 2020Published: March 24, 2021

https://doi.org/10.18632/aging.202793

Copyright: © 2021 Peng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Annexin A4 (ANXA4) is a Ca²⁺- and phospholipid-binding protein that belongs to the annexin family, which is involved in the development of multiple tumour types via NF-κB signalling. In this study, we verified the high expression and membrane-cytoplasm translocation of ANXA4 in colorectal carcinoma (CRC). Calcium/calmodulin-dependent protein kinase II gamma (CAMK2γ) was found to be important for high ANXA4 expression in CRC, whereas carbonic anhydrase (CA1) promoted ANXA4 aggregation in the cell membrane. An increased Ca²⁺ concentration attenuated the small ubiquitin-like modifier (SUMO) modification of cytoplasmic ANXA4 and ANXA4 stabilization, and relatively high expression of ANXA4 promoted CRC tumorigenesis and epithelial-mesenchymal transition (EMT).