ZG16B: A key regulator of tumor progression and immune microenvironment modulation in cancer (Review)
Xing-Ming Chen, Yu-Bo Liang, Jin-Xiang Zuo, Zisheng Yang, Le-Yu Zhang, Xin-Yu Zhang, Ping Wan, Yang Ke
Abstract
Zymogen granule protein 16B (ZG16B), also known as pancreatic adenocarcinoma upregulated factor, is a secretory lectin‑like glycoprotein that serves a crucial role in tumorigenesis and immune regulation. The present review summarizes the latest research progress on the molecular characteristics, biological functions, signaling pathway regulation and clinical importance of ZG16B. Structurally, ZG16B contains an N‑terminal hydrophobic signal peptide, a jacalin‑related lectin domain and a C‑terminal extension. Functionally, ZG16B promotes tumor cell proliferation, migration, invasion and angiogenesis, and increases vascular permeability by activating the Toll‑like receptor, C‑X‑C chemokine receptor type 4, β‑catenin and focal adhesion kinase signaling pathways. In the tumor microenvironment, ZG16B can modulate immune responses, enhance the immunosuppressive functions of myeloid‑derived suppressor cells and M2 macrophages, and also promote the maturation of dendritic cells. Clinically, ZG16B expression is upregulated in pancreatic cancer, ovarian cancer, colorectal cancer, gastric cancer and oral cancer, and its upregulation is associated with a worse prognosis in these malignancies. Several ZG16B‑specific therapeutic strategies, including monoclonal antibodies, RNA aptamers and trans‑splicing ribozymes, have shown preclinical efficacy against malignant tumors. Furthermore, a clinical trial is currently testing the efficacy and safety of PBP1510, a humanized ZG16B antibody, for the treatment of advanced pancreatic cancer. In conclusion, ZG16B may be considered a novel target for cancer diagnosis, prognosis and therapy.