Related Experiment Video
Updated: May 30, 2026

Aip1p Dynamics Are Altered by the R256H Mutation in Actin
Published on: July 30, 2014
Calpain 2 Isoform-Specific Cleavage of Filamin A Enhances HIF1α Nuclear Translocation, Promoting Metastasis in
Kyung-Hwa Jeon1,2, Seojeong Park1, Eun Seon Pak1,2
1College of Pharmacy Graduate School of Pharmaceutical Sciences Ewha Womans University Seoul Republic of Korea.
Abstract:
Triple-negative breast cancer (TNBC) remains a challenge due to its aggressive nature and limited therapeutic options. Calpain 2, a member of the calcium-dependent cysteine protease family, is particularly associated with poor prognosis in TNBC. This study explores the isoform-specific role of calpain 2 in TNBC, examining its correlation with prognosis and its mechanistic impact on metastasis. Bioinformatic analyses, including Kaplan-Meier survival plots, univariate Cox proportional analysis, and gene set enrichment analysis (GSEA), assessed CAPN2 expression and its association with mesenchymal genes in TNBC. Results of cell-based experiments with CAPN2 knockdown or overexpression indicate that elevated CAPN2 expression correlates with poor clinical outcomes and enhanced metastatic potential in TNBC. CAPN2 knockdown inhibited the epithelial-mesenchymal transition (EMT), reducing cancer cell proliferation, migration, and invasion. Calpain 2 downregulation reversed the EMT by reducing isoform-specific cleavage of filamin A, HIF1α nuclear localization and TWIST1 transcription. CNa 29, a calpain 2-specific inhibitor, reduced cancer cell proliferation, decreased filamin A cleavage, downregulated TWIST1 expression, and significantly retarded metastasis,. In conclusion, calpain 2 plays a critical role in TNBC progression by modulating HIF1α and TWIST1, to promote the EMT and metastasis. Isoform-selective inhibition of calpain 2 with CNa 29 presents a promising therapeutic strategy for managing TNBC.
More Related Videos
09:52A Chromatin Immunoprecipitation Assay to Identify Novel NFAT2 Target Genes in Chronic Lymphocytic Leukemia
Published on: December 4, 2018
06:27A 3D Spheroid Model as a More Physiological System for Cancer-Associated Fibroblasts Differentiation and Invasion In Vitro Studies
Published on: August 8, 2019
Related Concept Videos
Actin Filament Depolymerization
In F-actin, the ADF/cofilin proteins...
Formation of Higher-order Actin Filaments
The high-order actin networks...
Mechanism of Filopodia Formation
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Cancer Cell Migration through Invadopodia
Caspases
Regulation of Angiogenesis and Blood Supply