ArticleMolecular oncology2016
KLK6-regulated miRNA networks activate oncogenic pathways in breast cancer subtypes.
Article in Molecular oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Article
- Article
- HSP90α and KLK6 Co-Regulate Stress-Induced Prostate Cancer Cell Motility.bioRxiv : the preprint server for biology · 2025Article
- Plasma Circular RNAs in Breast Cancer: From Biomarker Potential to Functional Significance.Cancer reports (Hoboken, N.J.) · 2025Review
- Succinylation heterogeneity in lung adenocarcinoma: from prognostic model to KLK6-driven tumor microenvironment remodeling.Frontiers in immunology · 2025Article
- KLK7, KLK10, and KLK11 in Papillary Thyroid Cancer: Bioinformatic Analysis and Experimental Validation.Biochemical genetics · 2024Article
- Emerging roles and biomarker potential of WNT6 in human cancers.Cell communication and signaling : CCS · 2024Review
- Serine protease inhibitors decrease metastasis in prostate, breast, and ovarian cancers.Molecular oncology · 2023Article
- KLK6 Functions as an Oncogene and Unfavorable Prognostic Factor in Bladder Urothelial Carcinoma.Disease markers · 2022Article
- Biochemical pathways mediated by KLK6 protease in breast cancer.Molecular oncology · 2019Article
- Kallikrein 6 protease advances colon tumorigenesisOncotarget · 2019Article
- KLK6 Promotes Growth, Migration, and Invasion of Gastric Cancer Cells.Journal of gastric cancer · 2018Article
- Advances in circular RNAs and their roles in breast Cancer.Journal of experimental & clinical cancer research : CR · 2018Review
- A potent, proteolysis-resistant inhibitor of kallikrein-related peptidase 6 (KLK6) for cancer therapy, developed by combinatorial engineering.The Journal of biological chemistry · 2018Article
- Kallikrein-related peptidase 6 (KLK6) expression differentiates tumor subtypes and predicts clinical outcome in breast cancer patients.Clinical and experimental medicine · 2018Article
- Comprehensive circular RNA profiling reveals the regulatory role of the circRNA-000911/miR-449a pathway in breast carcinogenesis.International journal of oncology · 2018Article
- Prognostic role of miR-17-92 family in human cancers: evaluation of multiple prognostic outcomes.Oncotarget · 2017Review
- Identification of circular RNAs as a promising new class of diagnostic biomarkers for human breast cancer.Oncotarget · 2017Article
- Specific microRNA-mRNA Regulatory Network of Colon Cancer Invasion Mediated by Tissue Kallikrein-Related Peptidase 6.Neoplasia (New York, N.Y.) · 2017Article
- Evaluation Expression of Microrna-93 and Integrin Β8 in Different Types of Glioma TumorsAsian Pacific journal of cancer prevention : APJCP · 2017Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
KLK6 is expressed in normal mammary tissues and is aberrantly regulated in breast cancer. At physiological levels of expression, i.e. those found in normal mammary tissues, KLK6 acts as a tumor suppressor in human breast cancer. However, aberrant overexpression of KLK6 (i.e. 50-100-fold higher than normal), a characteristic of a subset of human breast cancers is associated with increased tumorigenicity (Pampalakis et al. Cancer Res 69:3779-3787, 2009). Here, we stably transfected KLK6-non-expressing MDA-MB-231 breast cancer cells with the full-length KLK6 cDNA to overexpress KLK6 at levels comparable to those observed in patients, and investigated potential oncogenic miRNA networks regulated by these abnormally high KLK6 expression levels and increased activity of this serine protease. A number of miRNAs that are upregulated (e.g. miR-146a) or downregulated (e.g. miR-34a) via KLK6-induced alterations in the miRNA biogenesis machinery were identified. Integrated experimental and bioinformatics analyses identified convergent miRNA networks targeting the cell cycle, MYC, MAPK, and other signaling pathways. In large clinical datasets, significant correlations between KLK6 and downstream MAPK and MYC targets at both the RNA and protein levels was confirmed, as well as negative correlation with GATA3. It was also demonstrated that KLK6 overexpression and likely its proteolytic activity is associated with alterations in downstream miRNAs and their targets, and these differ with the molecular subtypes of breast cancer. The data partly explains the different characteristics of breast cancer subtypes. Importantly, we introduce a combined KLK6-CDKN1B+MYC+CDKN1C score for prediction of long-term patient survival outcomes, with higher scores indicating poor survival.
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