bims-merabr Biomed News
on Metabolic rewiring in aggressive breast cancer
Issue of 2026–02–08
six papers selected by
Barbara Mensah Sankofi, University of Oklahoma Health Sciences Center
  1. Obesity- and tumor-derived signals drive cancer-associated state transitions in breast mesenchymal stromal/stem cells reprogrammed by IL1RA or JAK inhibition.
  2. CCNL1 Activates the NF-κB Pathway Through DVL3 Inhibition and PI3K/AKT Pathway Promotion in Breast Cancer.
  3. Integrated Analysis Reveals ZNF184 as a Novel Regulator of Stemness-Associated Paclitaxel Resistance and Tumor Progression in Breast Cancer.
  4. Oncogenic functions of polypyrimidine tract-binding protein 1 in breast cancer metabolism and progression.
  5. TMEM205 promotes M2-like macrophage polarization and advances the progression of triple-negative breast cancer.
  6. DSN1 drives breast cancer progression via cell cycle regulation: diagnostic and therapeutic implications.
  1. Exp Hematol Oncol. 2026 Feb 05. 15(1): 16
    Obesity- and tumor-derived signals drive cancer-associated state transitions in breast mesenchymal stromal/stem cells reprogrammed by IL1RA or JAK inhibition.
    Andreas Ritter, Samira Catharina Hoock, Nina-Naomi Kreis, Susanne Roth, Rosario Carolina Torres Colin, Alexandra Friemel, Julia Maria Wildner, Ilona Scherr, Frank Louwen, Christine Solbach, Juping Yuan.
      The tumor microenvironment (TME) in breast cancer is shaped by reciprocal interactions between cancer cells and their surrounding stromal populations. Here, we show that breast adipose tissue-derived stromal/stem cells (bASCs) undergo distinct state transitions in response to tumor cues and systemic metabolic status. Using primary bASCs derived from tumor-adjacent and tumor-distant adipose tissues of breast cancer patients with or without obesity, we identify two functionally distinct, tumor-educated stromal phenotypes: a cytokine-rich inflammatory CAF-like (iCAF) state predominating in lean-adjacent bASCs (ln-aT), and a myofibroblastic CAF-like (myCAF) state emerging in obese-adjacent bASCs (ob-aT). Importantly, transforming growth factor β (TGFβ) is sufficient to induce myCAF-like reprogramming in obesity-primed bASCs, while interleukin 1 (IL1)-Janus kinase (JAK) signaling promotes iCAF features. Re-analysis of single-cell RNA-seq data of breast cancer samples reveals an increased TGFβ expression across stromal and immune cell types in individuals with obesity. Mechanistically, IL1 receptor blockade (anakinra) or JAK inhibition (AZD1480) reverses both iCAF and myCAF phenotypes and functionally suppresses stromal-driven epithelial-mesenchymal transition as well as cancer stemness in breast cancer cells. These findings establish a mechanistic link between obese cues, stromal plasticity, and breast cancer progression, and reveal IL1/JAK signaling as a tractable axis to therapeutically reprogram the breast cancer stroma.
    Keywords:  Adipose tissue-derived mesenchymal stromal/Stem cells; Breast cancer; Cancer stem cells; Cancer-associated fibroblasts; Epithelial-to-mesenchymal transition; IL1/JAK pathway; Obesity; Stromal cell plasticity; TGFβ signaling
    DOI:  https://doi.org/10.1186/s40164-026-00747-7
  2. Mol Carcinog. 2026 Feb 03.
    CCNL1 Activates the NF-κB Pathway Through DVL3 Inhibition and PI3K/AKT Pathway Promotion in Breast Cancer.
    Dan Zhang, Runfen Cheng, Jiaxin Gao, Jiyuan Han, Chunsheng Ni, Song Wang, Xiulan Zhao, Baocun Sun, Tieju Liu.
      Cyclin L1 (CCNL1) is highly expressed in multiple cancer types and has been linked to poor prognosis. However, the expression pattern of CCNL1 in breast cancer and its specific role in regulating breast cancer progression remain largely unknown. This study used cell and molecular biology techniques to examine how CCNL1 regulates the proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) of breast cancer cells. The applied methods encompassed plasmid transfection, Transwell assay, wound-healing assay, Western blot analysis, co-immunoprecipitation (Co-IP), and rescue assay. For the analysis of CCNL1-related factors and pathways, bioinformatics platforms including Metascape and HURI were also employed. CCNL1 is highly expressed in breast cancer cells and is associated with a poor prognosis. CCNL1 overexpression increased breast cancer cell invasion and migration and accelerated proliferation. Overexpression of CCNL1 was found to upregulate the mesenchymal marker Vimentin and downregulate the epithelial marker E-cadherin expression. There is close relationship between CCNL1, the NF-κB and PI3K/AKT signaling pathways. The direct interaction is verified between CCNL1 and DVL3 by Co-IP, indicating a negative correlation between the two proteins. CCNL1 overexpression affects breast cancer cells' paclitaxel sensitivity through the PI3K/AKT pathway. CCNL1 activates the NF-κB signaling pathway through its interaction with DVL3; additionally, it promotes the PI3K/AKT pathway. Together, these two mechanisms enable CCNL1 to exert a regulatory role in the progression of breast cancer.
    Keywords:  CCNL1; DVL3; NF‐κB; PI3K/AKT; breast cancer
    DOI:  https://doi.org/10.1002/mc.70090
  3. Mol Carcinog. 2026 Feb 05.
    Integrated Analysis Reveals ZNF184 as a Novel Regulator of Stemness-Associated Paclitaxel Resistance and Tumor Progression in Breast Cancer.
    Rong Gong, Yizhi Li, Xiaoya Wan, Shilong Jiang, Deyang Wang, Qi Fu, Anze Yang, Yidi Guan, Ruigang Zhao, Yan Cheng.
      Chemotherapy resistance is the primary cause of clinical treatment failure and unfavorable prognosis among breast cancer patients. Consequently, the exploration of novel molecular targets for chemotherapy resistance is warranted. Here, we demonstrated that Zinc Finger Protein 184 (ZNF184) facilitates chemoresistance in breast cancer. Through integrated bioinformatics and experimental validation, we identified that ZNF184 was highly expressed in paclitaxel-resistant breast cancer cells. Knockdown of ZNF184 inhibited cell proliferation and re-sensitized resistant cells to paclitaxel in vitro and in patients-derived organoids (PDOs). Mechanistically, ZNF184 regulates the expression of stemness-related genes CD44, OCT4, Nanog, SOX2, and ALDH1A1, thereby promoting the proliferation of breast cancer cells and subsequent paclitaxel resistance. Pan-cancer analysis revealed the potential of ZNF184 as a prognostic and predictive biomarker for adverse clinical outcomes. Collectively, these findings reveal a previously unknown role of ZNF184 in breast cancer progression and paclitaxel resistance, providing new insights into ZNF184 as a potential therapeutic target for cancer patients.
    Keywords:  ZNF184; breast cancer; paclitaxel resistance; stemness
    DOI:  https://doi.org/10.1002/mc.70088
  4. Biochem Biophys Rep. 2026 Mar;45 102458
    Oncogenic functions of polypyrimidine tract-binding protein 1 in breast cancer metabolism and progression.
    Manabu Futamura, Yoshihisa Tokumaru, Akira Nakakami, Yoshimi Niwa, Junichi Mase, Emiri Sugiyama, Mai Okawa, Kana Matsuda, Ryutaro Mori, Yukihiro Akao, Nobuhisa Matsuhashi.
      Polypyrimidine tract-binding protein 1 (PTBP1) is an RNA-binding protein that regulates alternative splicing and primarily acts as a splicing repressor. Previous studies have shown that PTBP1 is closely linked to cancer metabolism through regulation by miR-133b and miR-124, which inhibit PTBP1 expression and modulate the splicing of the pyruvate kinase muscle (PKM) gene. Increased PTBP1 expression promotes PKM2 production and enhances glycolysis-dependent metabolism, a hallmark of cancer known as the Warburg effect. Clinical and experimental analyses were conducted to investigate the role of PTBP1 in breast cancer (BC). In silico investigations using The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets revealed a significant association between PTBP1 overexpression and poor prognosis. In vitro, PTBP1 knockdown in BC cell lines (MCF7, SK-BR-3, and MDA-MB-231) increased PKM1 expression and the PKM1/PKM2 ratio, leading to reduced cell proliferation. ATP production increased in MCF7 and SK-BR-3 cells, but not in MDA-MB-231. Although NADH levels were elevated in MCF7 and MDA-MB-231 cells, lactate accumulation was most prominent in MDA-MB-231 cells. qRT-PCR analysis of surgical BC specimens confirmed significantly higher PTBP1 expression in tumour tissues than in adjacent normal breast tissues, with expression positively correlating with tumour grade. These findings collectively demonstrate that PTBP1 is overexpressed in BC and drives cancer-specific metabolic reprogramming associated with the Warburg effect. Therefore, PTBP1 may act as an oncogenic regulator of breast cancer metabolism and serve as a potential therapeutic target.
    Keywords:  Breast cancer; Glycolysis; Oncogene; PKM; PTBP1; Warburg effect
    DOI:  https://doi.org/10.1016/j.bbrep.2026.102458
  5. Breast Cancer Res Treat. 2026 Feb 06. 216(1): 1
    TMEM205 promotes M2-like macrophage polarization and advances the progression of triple-negative breast cancer.
    Yining Zhang, Jing Peng, Teng Ma, Xiangping Liu, Jiaxiu Liu, Quan Zhou, Haibo Wang.
       INTRODUCTION: Triple-negative breast cancer (TNBC) is a highly aggressive subtype and lacks effective targeted therapies. Transmembrane protein 205 (TMEM205) has been implicated in tumor progression and immune resistance, but its precise role and mechanism in TNBC remain unclear. This study aims to explore the function and mechanism of TMEM205 in TNBC progression, as well as its impact on the tumor immune microenvironment.
    METHODS: The expression and prognostic significance of TMEM205 in breast cancer were analyzed using datasets, such as TCGA and UALCAN. TMEM205 was overexpressed and knocked down in TNBC cell lines (MDA-MB-231 and BT-549), and the effects on cell biological activity were verified by functional assays, including CCK-8, colony formation, wound healing, and Transwell assays. A coculture system of tumor cells and THP-1-derived macrophages was established. Key signaling molecules of TNBC cells were detected by Western blot, and cytokine levels by ELISA, so as to study tumor cell-macrophage interactions. The role of TMEM205 in tumor growth and angiogenesis was further validated through xenograft mouse models and endothelial tube formation assays.
    RESULTS: TMEM205 was significantly upregulated in breast cancer tissues and associated with a poor prognosis. TMEM205 overexpression promoted the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of TNBC cells, while TMEM205 knockdown inhibited their biological functions. Furthermore, TMEM205 overexpression not only increased the secretion of IL-6 but also activated the JAK2/STAT3 signaling axis, showing a positive correlation with M2 macrophage infiltration. The TNBC cell-conditioned medium with TMEM205 overexpression significantly promoted endothelial cell angiogenesis.
    CONCLUSION: TMEM205, as a multifunctional oncoprotein in TNBC, jointly drives tumor progression by promoting cell proliferation, metastasis, angiogenesis, and fostering an immunosuppressive microenvironment via M2 macrophage polarization. TMEM205 may be a promising therapeutic target for TNBC.
    Keywords:  Angiogenesis; Breast cancer; M2 polarization; Prognosis; TMEM205
    DOI:  https://doi.org/10.1007/s10549-026-07911-x
  6. Front Oncol. 2025 ;15 1711214
    DSN1 drives breast cancer progression via cell cycle regulation: diagnostic and therapeutic implications.
    Dongyang Liu, Manuel A Luis, Djojomoenawi Sherilyn H G, Xiaoxuan Zhu, Xiuqin Zhang, Yuan Fang, Xiaoyan Lin, Shasha Tang, Fengfeng Cai.
       Aim: Breast cancer is the most prevalent form of cancer among females and carries a substantial societal impact. DSN1, a component of the MIS12 complex, plays a critical role in centromere assembly, distribution, and stability. While DSN1's role in tumors has been investigated, its specific function in breast cancer remains unclear.
    Methods: First, we utilized bioinformatics techniques to explore DSN1 expression in breast cancer and conducted functional enrichment and correlation analyses. Subsequently, we assessed the clinical relevance of DSN1 through immunohistochemistry. Furthermore, we examined how DSN1 affects the growth of breast cancer cells by conducting CCK8 and colony formation tests. Cell cycle and apoptosis changes were assessed using flow cytometry. Moreover, we examined key genes related to cell cycle and apoptosis to further elucidate the underlying mechanisms. Finally, we screened potential drugs targeting DSN1 by drug sensitivity and molecular docking analyses.
    Results: Bioinformatics analysis revealed that DSN1 is highly expressed in breast cancer, making it a potential diagnostic marker. Functional enrichment analysis indicated that the DSN1- overexpressed group was enriched in cell proliferation-related pathways. Cellular experiments confirmed that DSN1 promotes breast cancer proliferation by affecting cell cycle pathways, involving key molecules such as CCNB1, CCND1, CKD1, CDK4, and CDK6. Drug sensitivity analysis showed that the DSN1 high expression group was resistant to drugs such as Epirubicin, Cyclophosphamide, Ribociclib, and Palbociclib, but relatively sensitive to tamoxifen and lapatinib.
    Conclusions: DSN1 contributes to breast cancer progression by modulating cell cycle pathways, making it a potential diagnostic and therapeutic target with clinical applicability.
    Keywords:  DSN1; breast cancer; cell cycle; cell proliferation; drug sensitivity
    DOI:  https://doi.org/10.3389/fonc.2025.1711214
This page is being maintained by Thomas Krichel. It was last updated on 2026‒02‒08 at 0:26.