bims-merabr Biomed News
on Metabolic rewiring in aggressive breast cancer
Issue of 2025–06–08
seven papers selected by
Barbara Mensah Sankofi, University of Oklahoma Health Sciences Center
  1. The Role of FGFR2 on Proliferation, Apoptosis and Glucose Metabolism of Breast Cancer Cells.
  2. METTL14-Mediated M6A Modification of LINC01094 Induces Glucose Metabolic Reprogramming in Breast Cancer by Recruiting the PKM2/JMJD5 Complex.
  3. CD151 Promotes Cancer Progression in Triple-Negative Breast Cancer by Inducing EMT through the MAPK Signaling Pathway.
  4. SENP5 drives breast cancer progression through deSUMOYlation of CDK1.
  5. Metastatic breast cancer cells adapt to a soft environment with limited involvement of mechanotransduction.
  6. The deubiquitinase USP7 stabilizes HER2 expression and promotes breast cancer progression.
  7. Mouse Models of Breast Cancer Bone Metastasis.
  1. Crit Rev Immunol. 2025 ;45(3): 51-62
    The Role of FGFR2 on Proliferation, Apoptosis and Glucose Metabolism of Breast Cancer Cells.
    Yuan Liang, Tian-Cheng Ma, Junhui Qin, Yuwei Li, RuiAn Wang.
      The present study investigated the expression of miR-598 in both breast cancer tissues and cells. Overexpression systems were established by introducing miR-598 mimics and pcDNA- Fibroblast Growth Factor Receptor 2(FGFR2) plasmids, either individually or in combination, into breast cancer cells. Four groups were constituted for probing purposes: control group, miR-598 mimics group, pcDNA-FGFR2 group, and mimics+FGFR2 group. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to measure the expression of miR-598 and FGFR2. Furthermore, bioinformatics software was used to predict and identify the possible binding sites between miR-598 and FGFR2. To validate the predicted binding sites, a dual-luciferase reporter gene experiment was carried out. A clone formation assay was used to evaluate cell proliferation, while glucose consumption and lactic acid production assays were conducted using a kit. Moreover, Western blot analysis was done to ascertain the expression of Bcl-2, Bax, Caspase-3, and Caspase-9 proteins. The expression of miR-598 in breast cancer tissues and cell lines was found to be significantly lower than that in normal breast tissues and cell lines, respectively (P < 0.05). It was also revealed that FGFR2 is the target gene of miR-598 and there is an inverse correlation between the two. Overexpression of miR-598 led to a decrease in clonal formation rate caused by high FGFR2 levels. Moreover, the overexpression of miR-598 reversed the effects induced by high FGFR2 levels, such as increased mitochondrial membrane potential and reduced expression of apoptosis-associated proteins. The microRNA miR-598 has been found to decrease the proliferation of breast cancer cells by targeting FGFR2, inducing apoptosis, and suppressing glucose consumption.
    DOI:  https://doi.org/10.1615/CritRevImmunol.2025054378
  2. Adv Sci (Weinh). 2025 Jun 05. e10386
    METTL14-Mediated M6A Modification of LINC01094 Induces Glucose Metabolic Reprogramming in Breast Cancer by Recruiting the PKM2/JMJD5 Complex.
    Mengqi Wang, Zhaoxin Gao, Ruinan Zhao, Pan Zhou, Jingxi Chen, Hui Zhang, Yawen Wang, Wenjie Zhu, Peng Gao.
      Tumor cells reprogram their energy metabolism patterns to meet the needs of rapid growth and metastasis. The underlying mechanisms of long noncoding RNAs (lncRNAs) in glucose metabolism remodeling in breast cancer (BC) are still not well understood. Herein, the expression of a tumorigenic lncRNA, LINC01094 are demonstrated that, is significantly increased in BC tissues and is associated with poorer patient survival. METTL14-mediated m6A modification stabilized LINC01094 by recruiting the reader protein IGF2BP2, which contributed to the upregulation of LINC01094 expression in BC. Gain- and loss-of-function assays validated that LINC01094 triggered a switch in glucose metabolism from mitochondrial respiration to glycolysis, promoting BC progression both in vitro and in vivo. LINC01094 promoted the dimeric assembly and nuclear translocation of PKM2 by acting as a "molecular scaffold" for the PKM2/JMJD5 complex. This, in turn, facilitated energy metabolic reprogramming and cell proliferation induced by HIF1-α/β-catenin. Furthermore, the therapeutic potential of LINC01094 is evaluated through the administration of the PKM2 activator TEPP-46 in mouse xenografts. These findings highlight the critical roles of LINC01094 in cellular glucose metabolism and tumorigenesis in BC, suggesting that it is a potential therapeutic target.
    Keywords:  LINC01094; PKM2; breast cancer; glucose metabolic reprogramming; m6A modification
    DOI:  https://doi.org/10.1002/advs.202410386
  3. Breast Cancer (Dove Med Press). 2025 ;17 455-470
    CD151 Promotes Cancer Progression in Triple-Negative Breast Cancer by Inducing EMT through the MAPK Signaling Pathway.
    Haishu Lv, Beibei Zhang, Xi Weng, Youjia Li, Chaoxian Deng, Rui Wang, Lei Shi, Yuanqin Yin.
       Background: Breast cancer has become one of the most prevalent malignant neoplasms among women, poses a significant threat to public health. As a member of the tetraspanin family of proteins, CD151 is implicated in tumor progression and has been shown to regulate various cellular and molecular mechanisms that drive malignancy. However, the specific functions of CD151 in triple-negative breast cancer (TNBC) remain unclear. In this study, we aimed to investigate the pro-tumorigenic role of CD151 in TNBC by focusing on its interaction with integrin α3β1, which often forms a complex with CD151.
    Methods: Our study first evaluated CD151 expression in clinical samples from TNBC patients and TNBC cell lines by immunohistochemistry and Western blotting analysis. Through RNA interference (RNAi) and constructed overexpressed plasmids, we further validated the impact of CD151 on the migration and invasion of TNBC cells. Then the differentially expressed genes were screened by single-cell RNA sequencing, and these genes were enriched and analyzed. Co-immunoprecipitation studies demonstrated the binding of CD151 with integrin α3β1. Western blotting analysis was used to evaluate the expression of proteins related to epithelial-mesenchymal transition (EMT) and Mitogen-activated protein kinase (MAPK) signaling pathway.
    Results: CD151 is highly expressed in TNBC tissues and cell lines. It enhanced the migration and invasive ability of TNBC cells by promoting EMT. Co-IP demonstrated the binding of CD151 and integrin α3β1. In addition, we found that knockdown of either integrin α3β1 or CD151 reduced the migration and invasion of TNBC cells in vitro. Western blot analysis revealed that the CD151-integrin α3β1 complex could activate the MAPK signaling pathway in TNBC cells, subsequently leading to EMT of these cells.
    Conclusion: Based on our findings, we propose a novel mechanism by which CD151 mediates tumor progression through the initiation of EMT. This suggests that CD151 could be considered a potential therapeutic target for TNBC.
    Keywords:  CD151; EMT; MAPK signaling pathway; TNBC; integrin α3β1
    DOI:  https://doi.org/10.2147/BCTT.S518760
  4. Breast Cancer Res. 2025 Jun 05. 27(1): 100
    SENP5 drives breast cancer progression through deSUMOYlation of CDK1.
    Cui Chen, Hanming Yao, Haiqing Jie, Zhenkang Liang, Yuxuan Zhang, Xinyun Wen, Jinze Zhao, Huiping Xiong, Zongheng Zheng, Juekun Wu.
       BACKGROUND: Breast cancer (BRCA) remains a significant global health concern, with the need for novel therapeutic targets to improve patient outcomes. The role of the SENP family of de-SUMOylating enzymes in BRCA is not yet fully understood.
    METHODS: The expression and prognostic value of SENP family in BRCA were analyzed using the TCGA database. GSEA was conducted to identify correlations between SENP5 expression and cell cycle pathways. Experiments including Western blotting, RT-qPCR, CCK8 assays, colony formation assays, EdU staining, wound healing assays, and transwell assays were used to assess the impact of SENP5 knockdown on BRCA cell proliferation, migration, and invasion. Co-immunoprecipitation and fluorescence co-localization studies were employed to investigate the interaction between SENP5 and CDK1. The effects of combining SENP5 knockdown with CDK1 inhibition were evaluated in MDA-MB-231 xenograft mouse model.
    RESULTS: SENP5 was found to be overexpressed in BRCA and associated with poor prognosis. Knockdown of SENP5 significantly inhibited BRCA cell proliferation and migration. GSEA revealed a strong correlation between SENP5 and the cell cycle, particularly the G2M checkpoint and E2F target pathways. SENP5 was shown to promote cell cycle progression by upregulating CDK1. Mechanistically, SENP5 mediates the de-SUMOylation of CDK1, reducing its degradation via the ubiquitin-proteasome pathway and increasing CDK1 expression. In vivo, the combination of SENP5 knockdown and CDK1 inhibition significantly suppressed BRCA tumor growth.
    CONCLUSION: Our research identifies the SENP5/CDK1 axis as a key player in BRCA progression, highlighting its potential as a therapeutic target.
    Keywords:  Breast cancer; CDK1; Cell cycle; SENP5; SUMOylation
    DOI:  https://doi.org/10.1186/s13058-025-02054-1
  5. Exp Cell Res. 2025 Jun 02. pii: S0014-4827(25)00225-3. [Epub ahead of print]450(2): 114629
    Metastatic breast cancer cells adapt to a soft environment with limited involvement of mechanotransduction.
    Jun Kumai, Satoru Sasagawa, Yoshihiro Yui.
      The extracellular matrix (ECM) plays a crucial role in regulating intracellular signaling in tumor cells. Although the influence of ECM stiffness on tumor malignancy has been well studied, the adaptation of tumors to a soft extratumoral environment with an increasing proliferation rate remains poorly understood. In this study, we investigated the mechanism of tumor cell adaptation to a soft environment and its relationship with tumor malignancy. A soft extracellular environment was required for adaptation. Among the various cell lines, highly malignant cancer cells, such as MDA-MB-231, PC3 and KP4, demonstrated an adaptive response to soft environments, as evidenced by increased cell extension and proliferation. Furthermore, adaptation to a soft environment enhanced lung colonization in a mouse model of breast cancer, suggesting a potential link between adaptability to soft environments and accelerated tumor malignancy. The mechanical environment of the cells before being transferred to a softer environment affected their adaptation as a mechanical memory via histone modifications. Integrin β1-mediated adhesion to the ECM played a central role in this adaptive phenomenon. Interestingly, adaptation occurred through a mechanism with limited involvement of mechanotransduction and prominent enhancement of ribosomal activity, providing new insights into the proliferation mechanisms in a soft environment. This study revealed how tumor cells adapt to a soft environment and showed that the adaptation phenomenon may be related to malignant transformation. Thus, the adaptation mechanism may be a therapeutic target for the suppression of metastasis.
    Keywords:  Adaptation; Biophysics; Metastasis; Soft environment
    DOI:  https://doi.org/10.1016/j.yexcr.2025.114629
  6. Neoplasia. 2025 Jun 04. pii: S1476-5586(25)00072-7. [Epub ahead of print]66 101192
    The deubiquitinase USP7 stabilizes HER2 expression and promotes breast cancer progression.
    Xiaoyue He, Xiaohong Xia, Ziying Lei, Mengfan Tang, Jiangyu Zhang, Yuning Liao, Hongbiao Huang.
      The overexpression and amplification of HER2 occurs in breast cancer. However, the mechanism of HER2 action in tumor has not yet been elucidated. HER2 can be degraded by the UPS system, and several HER2-associated E3s have been identified, but the DUB for HER2 has not yet been uncovered. Targeted therapy against HER2 has achieved impressive efficacy in patients with HER2-positive breast cancer. Herein, using MTS, Western blot, Co-IP, colony formation, RT‒qPCR, EdU, flow cytometry, immunofluorescence assays and xenograft model, we elucidated that USP7 deletion inhibited the growth of HER2-positive breast cancer cell by decreasing HER2 protein abundance. We found that USP7 was highly expressed in HER2-positive breast cancer and the expression of USP7 and HER2 was positively correlated. USP7 overexpression accelerated cell cycle progression. Mechanistically, USP7 interacted with HER2 and decreased HER2 ubiquitination to stabilize its expression. Moreover, USP7 knockdown inhibited tumor growth in vivo and in vitro. In addition, HER2 overexpression partially reversed cell growth inhibition induced by USP7 inhibition. Analyses of clinical samples revealed that USP7 overexpression was associated with poor prognosis in patients with HER2+ breast cancer. Thus, this study revealed that USP7, as a DUB of HER2, may be a potential therapeutic target for patient with HER2+ breast cancer.
    Keywords:  Growth; HER2 Positive breast cancer; USP7; Ubiquitination
    DOI:  https://doi.org/10.1016/j.neo.2025.101192
  7. Methods Mol Biol. 2025 ;2885 399-421
    Mouse Models of Breast Cancer Bone Metastasis.
    Jiabao Zhou, Diane Lefley, Penelope Ottewell.
      This chapter aims to offer a thorough overview of mouse models used in the study of breast cancer bone metastasis. The primary emphasis is to guide researchers through the procedural steps essential for establishing and utilizing these models within their own studies. These detailed methods are aimed to help researchers acquire reliable, accurate, and meaningful results suitable for publication and subsequent translation into clinical advancements for women affected by breast cancer-induced bone metastasis.
    Keywords:  Bone metastasis; Breast cancer; Mouse
    DOI:  https://doi.org/10.1007/978-1-0716-4306-8_21
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