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RNA-Seq data for PyMT mammary tumor cells with or without LSD1-loss

ABSTRACT: LSD1 (KDM1A) is a histone demethylase. In human cancers, genetic abnormalities of LSD1 mainly include deletions and mutations; importantly, such deletions/mutations have also been found in metastatic breast cancers, raising a possibility that LSD1 is a breast cancer metastasis suppressor. We found induced loss of LSD1 in luminal mammary tumor cells in the MMTV-PyMT model led to a profound increase in lung metastasis. Intriguingly, PyMT tumor cells with LSD1-loss also exhibited a profound change in immune-related genes, suggesting that LSD1 may suppress breast cancer metastasis in part via a cell-extrinsic, immune mechanism. In particular, LSD1 disruption led to upregulation of expression of most MHC class I genes, which might cause reduced number, maturation and activation of NK cells. Reduced clearance of PyMT tumor cells with LSD1 disruption by NK cells might lead to their increased metastasis.

ORGANISM(S): Mus musculus

PROVIDER: GSE140820 | GEO | 2026/03/16

REPOSITORIES: GEO

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Project description:Background: Epithelial to mesenchymal transition (EMT) plays an essential role in the metastasis of breast cancer by regulating the migration and invasion of cancer cells. Lysine specific demethylase 1 (LSD1) is an important histone demethylase that mediates EMT. However, the functional effects of the mutation on LSD1 in breast cancer remain unclear. Results: An E239K mutation of LSD1 was identified from TCGA Breast Invasive Carcinoma cohort. To investigate the functional effects of the E239K mutation of LSD1, a stable LSD1 knockdown MCF7 cell line was generated. Rescue with the wild-type LSD1, but not the E239K mutated LSD1, suppressed the increased invasion of the LSD1 knockdown cells, demonstrating that the E239K mutation abolished the suppressive effects of LSD1 on the invasion of breast cancer cells. Further analysis showed that the E239K mutation of LSD1 led to decreased expression of estrogen receptor α (ERα), which subsequently increased the expression of Slug, a master transcription factor that promoted EMT. Most importantly, the E239K mutation of LSD1 disrupted the interaction between LSD1 and GATA3, which reduced the enrichment of LSD1 at the promoter region of ERα gene. The reduced enrichment of LSD1 at the promoter region of ERα gene caused enhanced histone H3K9 methylation, which in turn suppressed the transcription of ERα gene. Conclusions: The E239K mutation of LSD1 promotes the migration and invasion of breast cancer cells by disrupting the interaction between LSD1 and GATA3, which reduces the expression of ERα by enhancing the histone H3K9 methylation.

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