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WNK1 Enhances Migration and Invasion in Breast Cancer Models
- Source :
- Mol Cancer Ther
- Publication Year :
- 2021
- Publisher :
- American Association for Cancer Research (AACR), 2021.
-
Abstract
- Metastasis is the major cause of mortality in patients with breast cancer. Many signaling pathways have been linked to cancer invasiveness, but blockade of few protein components has succeeded in reducing metastasis. Thus, identification of proteins contributing to invasion that are manipulable by small molecules may be valuable in inhibiting spread of the disease. The protein kinase with no lysine (K) 1 (WNK1) has been suggested to induce migration of cells representing a range of cancer types. Analyses of mouse models and patient data have implicated WNK1 as one of a handful of genes uniquely linked to invasive breast cancer. Here, we present evidence that inhibition of WNK1 slows breast cancer metastasis. We show that depletion or inhibition of WNK1 reduces migration of several breast cancer cell lines in wound healing assays and decreases invasion in collagen matrices. Furthermore, WNK1 depletion suppresses expression of AXL, a tyrosine kinase implicated in metastasis. Finally, we demonstrate that WNK inhibition in mice attenuates tumor progression and metastatic burden. These data showing reduced migration, invasion, and metastasis upon WNK1 depletion in multiple breast cancer models suggest that WNK1 contributes to the metastatic phenotype, and that WNK1 inhibition may offer a therapeutic avenue for attenuating progression of invasive breast cancers.
- Subjects :
- Cancer Research
Pyrrolidines
Apoptosis
Breast Neoplasms
Mice, SCID
Biology
Article
Metastasis
Mice
Breast cancer
WNK Lysine-Deficient Protein Kinase 1
Cell Movement
Mice, Inbred NOD
Biomarkers, Tumor
Tumor Cells, Cultured
medicine
Animals
Humans
Neoplasm Invasiveness
Protein kinase A
Cell Proliferation
Imidazoles
Cancer
medicine.disease
WNK1
Xenograft Model Antitumor Assays
Gene Expression Regulation, Neoplastic
Oncology
Tumor progression
Cancer research
Female
Signal transduction
Tyrosine kinase
Subjects
Details
- ISSN :
- 15388514 and 15357163
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- Molecular Cancer Therapeutics
- Accession number :
- edsair.doi.dedup.....71ec8bf44396c3cc208c74eddff8e98f