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Abstract
The serine protease inhibitor Kazal type (SPINK) family includes SPINK1-14 and is the largest branch in the serine protease inhibitor family. SPINKs play an important role in pancreatic physiology and disease, sperm maturation and capacitation, Nager syndrome, inflammation and the skin barrier. Evidence shows that the unregulated expression of SPINK1, 2, 4, 5, 6, 7, and 13 is closely related to human tumors. Different SPINKs exhibit various regulatory modes in different tumors and can be used as tumor prognostic markers. This article reviews the role of SPINK1, 2, 4, 5, 6, 7, and 13 in different human cancer processes and helps to identify new cancer treatment targets.
Highlights
Serine protease inhibitors were first found in animal serum and are widely present in plants, animals, bacteria and viruses [1]
Analysis of short tandem repeats (STRs) in SPINK7 exon 4 in 86 patients with complete surgical resection found that the TCA3/TCA3 and TCA3/TCA4 genotypes both accounted for 47% of cases, the TCA4/TCA4 genotype accounted for 7% of cases, and the TCA3/TCA3 genotype was significantly associated with reduced survival rates [173]
Considering that SPINK5, SPINK6 and SPINK9 are all clustered on a chromosomal complex of 5q33, they are selective KLK inhibitors
Summary
Serine protease inhibitors were first found in animal serum and are widely present in plants, animals, bacteria and viruses [1]. The interaction between TIG1 and SPINK2 plays an important role in inhibiting the EMT of testicular cancer cells by downregulating the uPA/uPA receptor (uPAR) signaling pathway (Figure 2) [107]. Compared with that in normal esophageal tissue, the expression level of SPINK5 mRNA and protein in esophageal cancer tissue (including squamous cell carcinoma tissue) is significantly lower and predicts tumor lymph node metastasis and differentiation [137,138,139]. The loss of SPINK7 significantly enhanced the association between uPAR and beta integrin, increased the basal activation of the Src/MAPK pathway, and stimulated the migration and invasion of human fibrosarcoma cells and breast cancer cells [179]. SPINK13 inhibits cell proliferation, migration and EMT by inhibiting uPA [211]
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