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<p>Cellular senescence is a cell state characterized by a generally permanent cell-cycle arrest, generating a broad secretome of inflammatory factors, contributing to pro-inflammatory milieu. Pyroptosis is a lytic and highly regulated cell death mechanism with pro-inflammatory characteristics, mediated by gasdermin (GSDM) family of proteins, which has six members in humans: GSDMA-E and PJVK&#xa0;(GSDMF). The interplay between senescence and pyroptotic cell death has been shown in some contexts; however, crosstalk between senescence and pyroptosis has not been studied in breast cancer. In the present study, it was found that breast tumors with high gasdermin expression have higher expression of senescence marker genes, namely CDKN1A (encoding p21), CDKN2A (encoding p16) and TP53 (encoding p53). This is especially true for high GSDMD- or GSDME-expressing breast tumors, which show higher mRNA levels of all three senescence marker genes. This high GSDM-dependent increases in the transcript levels of cellular senescence marker genes is more frequent in breast cancer than in non-malignant breast tissue, suggesting that the association between gasdermin family of genes and senesence marker genes in terms of expression levels is&#xa0;stronger in the case of tumor rather than normal tissue. This might point that, in breast cancer, pyroptosis and senescence might be associated; however, whether pyroptosis regulates senescence or vice versa, whether these two processes both reciprocally regulate and control each other, or even whether they share a &#xa0;common&#xa0;upstream regulatory pathway remain to be identified. These findings also support previous research demonstrating the promoting effect of pyroptosis on senesence, and that SASP (senescence-associated secretory phenotype) factors can induce GSDMD–dependent pyroptotic cell death in neighboring cells present in the same microenvironment, in certain contexts. Further mechanistic studies are required to better characterize the cellular and molecular connections between senescence and pyroptosis in breast cancer.</p>

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Transcript levels of cellular senescence marker genes are increased based on high expression of gasdermin family of genes in breast cancer

  • 期刊论文

  • 发表日期：

    2025年7月3日

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  • Caglar Berkel

摘要

Cellular senescence is a cell state characterized by a generally permanent cell-cycle arrest, generating a broad secretome of inflammatory factors, contributing to pro-inflammatory milieu. Pyroptosis is a lytic and highly regulated cell death mechanism with pro-inflammatory characteristics, mediated by gasdermin (GSDM) family of proteins, which has six members in humans: GSDMA-E and PJVK (GSDMF). The interplay between senescence and pyroptotic cell death has been shown in some contexts; however, crosstalk between senescence and pyroptosis has not been studied in breast cancer. In the present study, it was found that breast tumors with high gasdermin expression have higher expression of senescence marker genes, namely CDKN1A (encoding p21), CDKN2A (encoding p16) and TP53 (encoding p53). This is especially true for high GSDMD- or GSDME-expressing breast tumors, which show higher mRNA levels of all three senescence marker genes. This high GSDM-dependent increases in the transcript levels of cellular senescence marker genes is more frequent in breast cancer than in non-malignant breast tissue, suggesting that the association between gasdermin family of genes and senesence marker genes in terms of expression levels is stronger in the case of tumor rather than normal tissue. This might point that, in breast cancer, pyroptosis and senescence might be associated; however, whether pyroptosis regulates senescence or vice versa, whether these two processes both reciprocally regulate and control each other, or even whether they share a  common upstream regulatory pathway remain to be identified. These findings also support previous research demonstrating the promoting effect of pyroptosis on senesence, and that SASP (senescence-associated secretory phenotype) factors can induce GSDMD–dependent pyroptotic cell death in neighboring cells present in the same microenvironment, in certain contexts. Further mechanistic studies are required to better characterize the cellular and molecular connections between senescence and pyroptosis in breast cancer.