Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Targeting of MCL-1 in breast cancer associated fibroblasts reverses their myofibroblastic phenotype and pro-invasive properties Cancer associated fibroblasts (CAF) are a major cellular component of epithelial tumors. In breast cancers in particular these stromal cells have numerous tumorigenic effects in part due to their acquisition of a myofibroblastic phenotype. Breast CAFs (bCAFS) typically express MCL-1. We show here that targeting this regulator of mitochondrial integrity using a specific BH-3 mimetic promotes fragmentation of these organelles without inducing cell death. MCL-1 antagonism in primary bCAFs directly derived from human samples mitigates myofibroblastic features and decreases expression of genes involved in actomyosin organization and contractility, associated with a cytoplasmic retention of the transcriptional regulator, Yes-Associated Protein (YAP). Such treatment decreases bCAFs ability to promote cancer cells invasion in 3D co-culture assays. These effects are counteracted by an inhibitor of the mitochondrial fission protein DRP-1, which interacts with MCL-1 upon BH3 mimetic treatment. Our findings underscore the usefulness of targeting MCL-1 in breast cancer ecosystems, not only to favor death of cancer cells but also to counteract the tumorigenic activation of fibroblasts with which they co-evolve.

The authors declare no conflict of interest.
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The categories of this paper are: cell
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The categories of this paper are: bioinformatics
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The categories of this paper are: developmental
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The categories of this paper are: neuroscience
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The categories of this paper are: toxicology
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The categories of this paper are: behavior
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The categories of this paper are: paleontology
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The categories of this paper are: and
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The categories of this paper are: molecular
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The categories of this paper are: synthetic
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The categories of this paper are: genomics
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The categories of this paper are: ecology
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The categories of this paper are: communication
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The categories of this paper are: biophysics
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The categories of this paper are: genetics
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The categories of this paper are: physiology