Abstract
Alpha-fetoprotein (AFP) entrance into cancer cells is mediated by AFP receptors (AFPRs) and exerts malignant effects. Therefore, understanding the structure of AFPRs will facilitate the development of rational approaches for vaccine design, drug delivery, antagonizing immune suppression and diagnostic imaging to treat cancer effectively. Throughout the last three decades, the identification of universal receptors for AFP has failed due to their complex carbohydrate polymer structures. Here, we focused on the two types of binding proteins or receptors that may serve as AFPRs, namely, the A) mucin receptors family, and B) the scavenger family. We presented an informative review with detailed descriptions of the signal transduction, cross-talk, and interplay of various transcription factors which highlight the downstream events following AFP binding to mucin or scavenger receptors. We mainly explored the underlying mechanisms involved mucin or scavenger receptors that interact with AFP, provide more evidence to support these receptors as tumor AFPRs, and establish a theoretical basis for targeting therapy of cancer.
Highlights
Alpha-fetoprotein (AFP) plays an important role in inducing malignant transformation of cancer cells, regulating cell proliferation, migration, apoptosis and immune escape, and is used as clinical biomarker to diagnose hepatocellular carcinoma [1,2,3,4,5]
Due to their complex types, polymer structure and carbohydrate composition, AFP receptor (AFPR) have not yet been clearly identified, but according to reports of their functions in tumors, AFPRs may belong to the G protein-coupled receptors (GPCRs), mucin (MUC) receptor family, scavenger receptor (SR) families and other cell surface receptors
We have focused on two candidate receptor protein family termed the MUC receptor family and SR family
Summary
Alpha-fetoprotein (AFP) plays an important role in inducing malignant transformation of cancer cells, regulating cell proliferation, migration, apoptosis and immune escape, and is used as clinical biomarker to diagnose hepatocellular carcinoma [1,2,3,4,5]. High expression of MUC1 has been linked to cancer cell proliferation, invasion, metastasis, and apoptosis inhibition This function of MUC1 is similar to that of AFPR, and it is possible that MUC1 can bind and be activated by AFP, which leads to phosphorylation of the cytoplasmic tail of MUC1 and the promotion of AFP endocytosis to activate related pathways [9, 30, 34, 45, 74]. AFP binding to ErbB2 can enhance MUC4 interactions with ErbB2, ErbB3, and neuregulin, increase the phosphorylation of the ErbB2 complex and result in enhancing cancer cell proliferation, migration, invasion and inhibition of apoptosis through activating ERK and AKT signaling pathways [74, 78, 79] (Figure 6). These SRs can form cooperative complexes with the Tolllike receptor-2 (TRL2) results in enhancing endocytosis of AFP, receptor signaling and cross-presentation of antigens for T cell activation [33, 100]
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