ANXA10

ANXA10 Full Name

annexin A10

ANXA10 Introduction

ANXA10 (annexin A10) is a member of the annexin superfamily of calcium-dependent phospholipid-binding proteins, which are involved in diverse cellular processes including membrane trafficking, exocytosis, endocytosis, signal transduction, and the regulation of inflammation and apoptosis. The annexin family comprises 12 members in humans (ANXA1-ANXA13, with ANXA12 being a pseudogene), each characterized by a conserved C-terminal core domain containing four (or eight in the case of ANXA6) annexin repeats of approximately 70 amino acids that mediate calcium-dependent membrane binding. Unlike most annexins that are ubiquitously expressed, ANXA10 exhibits a highly restricted tissue distribution, with highest expression detected in the stomach, particularly in the gastric epithelium, as well as in the liver, kidney, and certain cancer types. ANXA10 has emerged as an important biomarker for gastric cancer differentiation and prognosis, as well as a potential tumor suppressor in various malignancies. Its unique expression pattern and functional properties distinguish ANXA10 from other annexin family members and point to specialized roles in gastric homeostasis and carcinogenesis.

Figure 1. Schematic structure of ANXA10.

Tissue Distribution and Biological Functions in the Stomach
ANXA10 exhibits a highly restricted tissue distribution, with expression predominantly confined to the stomach, specifically in the mature surface epithelial cells and gastric foveolar cells of the gastric mucosa. This restricted expression pattern suggests specialized functions in gastric epithelial homeostasis. Within the stomach, ANXA10 expression is regulated during gastric epithelial cell differentiation, with expression increasing as cells mature and migrate toward the luminal surface. ANXA10 functions as a key regulator of gastric epithelial differentiation and the maintenance of the gastric mucosal barrier. It participates in the regulation of mucin secretion from gastric foveolar cells, contributing to the formation of the protective mucus layer that shields the gastric epithelium from acid, pepsin, and ingested pathogens. ANXA10 also plays a role in the repair of gastric mucosal injury by facilitating membrane remodeling and cell migration. In addition to the stomach, lower levels of ANXA10 expression have been detected in the liver (hepatocytes), kidney (proximal tubules), and certain regions of the brain. In the liver, ANXA10 may participate in bile secretion and hepatocyte polarity. In the kidney, ANXA10 expression is restricted to the proximal tubular epithelium, where it may be involved in endocytosis and the recycling of membrane proteins. The functional redundancy between ANXA10 and other annexins in non-gastric tissues is not fully understood, but the unique expression pattern suggests non-redundant functions in the stomach.

Role as a Biomarker and Tumor Suppressor in Gastric Cancer
ANXA10 has emerged as an important biomarker for gastric cancer differentiation and prognosis. In normal gastric mucosa, ANXA10 is highly expressed in differentiated surface epithelial cells but is significantly downregulated or completely lost in gastric cancer tissues. The loss of ANXA10 expression correlates with poor differentiation (higher grade), advanced tumor stage, lymph node metastasis, and shorter patient survival. Importantly, ANXA10 expression is retained in well-differentiated gastric cancers but is progressively lost as tumors become moderately or poorly differentiated, making ANXA10 a reliable immunohistochemical marker for gastric cancer differentiation status. Mechanistically, ANXA10 functions as a tumor suppressor in the stomach by promoting gastric epithelial differentiation and suppressing the epithelial-mesenchymal transition (EMT). ANXA10 maintains the expression of E-cadherin, a key cell-cell adhesion protein, and suppresses the expression of mesenchymal markers including vimentin and N-cadherin. ANXA10 also inhibits the activation of oncogenic signaling pathways including Wnt/beta-catenin, PI3K/AKT, and MAPK/ERK, which drive gastric cancer proliferation, survival, and invasion. The loss of ANXA10 expression in gastric cancer occurs primarily through promoter hypermethylation, an epigenetic silencing mechanism. Hypermethylation of the ANXA10 promoter region has been detected in a high percentage of primary gastric cancers and correlates with reduced ANXA10 mRNA and protein expression. This epigenetic silencing is reversible with DNA methyltransferase inhibitors such as 5-azacytidine and decitabine, which restore ANXA10 expression and suppress gastric cancer cell growth in preclinical models.

Alternate Names for ANXA10

ANXA10; annexin A10; ANX14; annexin 14; annexin-10; annexin-14;