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Review
. 2021 Apr 7;22(8):3814.
doi: 10.3390/ijms22083814.

Functional Roles of SPINK1 in Cancers

Tsung-Chieh Lin  1
Affiliations
Review

Functional Roles of SPINK1 in Cancers

Tsung-Chieh Lin. Int J Mol Sci. .

Abstract

Serine Peptidase Inhibitor Kazal Type 1 (SPINK1) is a secreted protein known as a protease inhibitor of trypsin in the pancreas. However, emerging evidence shows its function in promoting cancer progression in various types of cancer. SPINK1 modulated tumor malignancies and induced the activation of the downstream signaling of epidermal growth factor receptor (EGFR) in cancer cells, due to the structural similarity with epidermal growth factor (EGF). The discoverable SPINK1 somatic mutations, expressional signatures, and prognostic significances in various types of cancer have attracted attention as a cancer biomarker in clinical applications. Emerging findings further clarify the direct and indirect biological effects of SPINK1 in regulating cancer proliferation, metastasis, drug resistance, transdifferentiation, and cancer stemness, warranting the exploration of the SPINK1-mediated molecular mechanism to identify a therapeutic strategy. In this review article, we first integrate the transcriptomic data of different types of cancer with clinical information and recent findings of SPINK1-mediated malignant phenotypes. In addition, a comprehensive summary of SPINK1 expression in a pan-cancer panel and individual cell types of specific organs at the single-cell level is presented to indicate the potential sites of tumorigenesis, which has not yet been reported. This review aims to shed light on the roles of SPINK1 in cancer and provide guidance and potential directions for scientists in this field.

Keywords: SPINK1; carcinogenesis; prognosis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Human Serine peptidase inhibitor Kazal type I (SPINK1) isoform view. The data were retrieved and analyzed from Refseq. The matching protein domains in various RNA isoforms are marked and located in orange. The start of transcription and position of a stop codon are indicated by green and red arrowheads, respectively.
Figure 2
Figure 2
SPINK1 expression in single-cell types. The SPINK1 expression level was analyzed by single-cell RNA sequencing (scRNA-seq) using different human tissues (The Human Protein Atlas_ https://www.proteinatlas.org/, accessed on January 2021). RNA expression in the single-cell-type clusters identified in each tissue was visualized by a UMAP (Uniform Manifold Approximation and Projection) plot (top) and a bar chart (bottom). The read counts were normalized to transcripts per million protein-coding genes (pTPM) for each of the single-cell clusters.
Figure 3
Figure 3
SPINK1 expression view in a pan-cancer panel. In a pan-cancer dataset, SPINK1 expression levels were presented separately for 32 cancer types. The red color in the heat map represents high SPINK1 expression. The blue color in the heat map represents low SPINK1 expression. The raw data were retrieved from The Cancer Genome Atlas (TCGA) database.
Figure 4
Figure 4
The representative scheme of SPINK1 in cancer progression was shown.
See this image and copyright information in PMC

References

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