ArticleEMBO molecular medicine2011
Combined genomic and phenotype screening reveals secretory factor SPINK1 as an invasion and survival factor associated with patient prognosis in breast cancer.
Article in EMBO molecular medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 56 citations in OpenAlex.
- SPINK1 immunohistochemistry: An ancillary tool to diagnose urothelial carcinoma in situ and urothelial dysplasia.Pathology, research and practice · 2025Article
- The SPINK Protein Family in Cancer: Emerging Roles in Tumor Progression, Therapeutic Resistance, and Precision Oncology.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Male Breast Cancer Brain Metastases: Genetic Profiles and Radiosurgery Outcomes.Neurosurgery practice · 2025Article
- Three-Dimensional Structure of Novel Liver Cancer Biomarker Liver Cancer-Specific Serine Protease Inhibitor Kazal (LC-SPIK) and Its Performance in Clinical Diagnosis of Hepatocellular Carcinoma (HCC).Diagnostics (Basel, Switzerland) · 2024Review
- Association of clinicopathologic and molecular factors with the occurrence of positive margins in breast cancer.Breast cancer research and treatment · 2024Article
- SPINK1-induced tumor plasticity provides a therapeutic window for chemotherapy in hepatocellular carcinoma.Nature communications · 2023Article
- Article
- Raised SPINK1 levels play a role in angiogenesis and the transendothelial migration of ALL cells.Scientific reports · 2022Article
- SPINK1 contributes to proliferation and clonal formation of HT29 cells through Beclin1 associated enhanced autophagy.Oncology research · 2022Article
- SPINKs in Tumors: Potential Therapeutic Targets.Frontiers in oncology · 2022Review
- SPINK1 as a plasma marker for tumor hypoxia and a therapeutic target for radiosensitization.JCI insight · 2021Article
- Increased gene expression variability in BRCA1-associated and basal-like breast tumours.Breast cancer research and treatment · 2021Article
- Targeting an autocrine IL-6-SPINK1 signaling axis to suppress metastatic spread in ovarian clear cell carcinoma.Oncogene · 2020Article
- Article
- The Role of Serine Peptidase Inhibitor Kazal Type 13 (SPINK13) as a Clinicopathological and Prognostic Biomarker in Patients with Clear Cell Renal Cell Carcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- Epigenetic Silencing of miRNA-338-5p and miRNA-421 Drives SPINK1-Positive Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Hepatitis B Virus X Protein-Induced Serine Protease Inhibitor Kazal Type 1 Is Associated with the Progression of HBV-Related Diseases.BioMed research international · 2019Article
- Bad Tumors Made Worse: SPINK1.Frontiers in cell and developmental biology · 2019Article
- Identification of genes associated with matrix metalloproteinases in invasive lung adenocarcinoma.Oncology letters · 2018Article
- Transposon mutagenesis identifies genes that cooperate with mutant Pten in breast cancer progression.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Secretory factors that drive cancer progression are attractive immunotherapeutic targets. We used a whole-genome data-mining approach on multiple cohorts of breast tumours annotated for clinical outcomes to discover such factors. We identified Serine protease inhibitor Kazal-type 1 (SPINK1) to be associated with poor survival in estrogen receptor-positive (ER+) cases. Immunohistochemistry showed that SPINK1 was absent in normal breast, present in early and advanced tumours, and its expression correlated with poor survival in ER+ tumours. In ER- cases, the prognostic effect did not reach statistical significance. Forced expression and/or exposure to recombinant SPINK1 induced invasiveness without affecting cell proliferation. However, down-regulation of SPINK1 resulted in cell death. Further, SPINK1 overexpressing cells were resistant to drug-induced apoptosis due to reduced caspase-3 levels and high expression of Bcl2 and phospho-Bcl2 proteins. Intriguingly, these anti-apoptotic effects of SPINK1 were abrogated by mutations of its protease inhibition domain. Thus, SPINK1 affects multiple aggressive properties in breast cancer: survival, invasiveness and chemoresistance. Because SPINK1 effects are abrogated by neutralizing antibodies, we suggest that SPINK1 is a viable potential therapeutic target in breast cancer.
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