| Annexin A10 (ANXA10) is a calcium- and phospholipid-binding member of the annexin A family that shows tissue-restricted expression and functions as a regulator of epithelial differentiation and tumor progression in gastrointestinal and hepatobiliary tissues. The protein possesses the conserved annexin core of repeated annexin domains that mediate Ca²⁺‑dependent phospholipid association, together with a distinctive N‑terminal region that contributes to its nuclear localization in gastric epithelium and to interactions with signaling partners that control cell-cycle progression and survival. In normal adult liver, a short liver‑specific isoform (ANXA10S) is expressed, and down‑regulation of ANXA10S in hepatocellular carcinoma correlates with vascular invasion, early recurrence and poor prognosis, particularly when combined with p53 mutation, indicating that adequate ANXA10 expression restrains invasive growth and that loss of ANXA10 synergizes with p53 pathway disruption to accelerate tumor progression. In gastric mucosa across multiple species, ANXA10 protein is specifically expressed in fetal and adult gastric epithelium and Brunner’s glands, and is commonly lost in areas with intestinal metaplasia, marking it as a gastric differentiation marker whose presence distinguishes gastric‑type epithelium from metaplastic intestinal‑type mucosa. Immunohistochemical analysis of large gastric carcinoma cohorts shows ANXA10 expression in roughly half of tumors, with high prevalence in diffuse‑type and mixed‑type gastric carcinoma and much lower expression in intestinal‑type tumors; in diffuse‑type gastric carcinoma, ANXA10 positivity associates with lower tumor stage, reduced lymph‑node metastasis and better five‑year survival, whereas in intestinal‑type carcinoma ANXA10 expression correlates with higher stage and poorer survival, revealing subtype‑specific roles in tumor biology. In oral squamous cell carcinoma, ANXA10 mRNA and protein are upregulated relative to normal mucosa, and siRNA‑mediated knockdown reduces proliferation through inactivation of ERK signaling and G1 phase arrest accompanied by upregulation of cyclin‑dependent kinase inhibitors, identifying ANXA10 as an indicator and driver of tumor-cell proliferation via MAPK/ERK pathway modulation. Annexin A10 also influences apoptosis and stress responses in papillary thyroid carcinoma: ANXA10 and its binding partner TSG101 are upregulated in carcinoma cell lines, ANXA10 knockdown inhibits proliferation, promotes apoptosis and inactivates MAPK/ERK signaling, and these effects are reversed by TSG101 overexpression, demonstrating that ANXA10 binds TSG101 and maintains MAPK/ERK pathway activity to support thyroid tumor growth. Across pancreatic precursor lesions and invasive pancreatic ductal adenocarcinoma, ANXA10 is consistently overexpressed in ductal epithelial cells of PanINs, IPMNs and PDACs but absent in normal ducts and most chronic pancreatitis, and co‑expression with CD24 in high‑grade neoplasia correlates with progression toward PDAC, supporting its use as an early marker of ductal transformation and precursor lesion advancement. In colorectal and other cancers, ANXA10 knockdown has been reported to induce ferroptosis by interfering with autophagy-mediated TFRC degradation and to reduce metastasis by limiting EMT‑linked pathways such as PLA2G4A/PGE2/STAT3, further highlighting its mechanistic role in controlling proliferation, survival, migration and EMT via defined signaling axes. |
