bims-merabr Biomed News
on Metabolic rewiring in aggressive breast cancer
Issue of 2026–02–01
eight papers selected by
Barbara Mensah Sankofi, University of Oklahoma Health Sciences Center
  1. Microenvironment Modulates Tumorigenicity of Breast Cancer Cells Depending on Hormone Receptor Status.
  2. Inhibition of Breast Cancer Bone Metastasis by LRP5-Overexpressing Osteocytes via the LIMA1/MYO5B Signaling Axis.
  3. LINC00511 Promotes Breast Cancer Cell Proliferation and Invasion by Mediating MYC-Mediated Regulation of VASP.
  4. The WISP1/Src/MIF Axis Promotes the Malignant Phenotype of Non-Invasive MCF7 Breast Cancer Cells.
  5. The Interaction of CircESR1 and HNRNPAB Regulates Cell Cycle Transition of Breast Cancer Cell.
  6. Exosome RAB10 inhibits JAK1/STAT1 to hinder macrophage M1 polarization and promote tumor immune escape.
  7. RUBCN as a novel prognostic biomarker and therapeutic target in breast cancer.
  8. USP30-AS1 Dictates Breast Cancer Cell Fate and Chemoresistance via a miR-3646/FZD7/Wnt/β-Catenin Circuit.
  1. Int J Mol Sci. 2026 Jan 22. pii: 1129. [Epub ahead of print]27(2):
    Microenvironment Modulates Tumorigenicity of Breast Cancer Cells Depending on Hormone Receptor Status.
    Priscila Pagnotta, Tomás González-Garello, María Luján Crosbie, Natalia Santiso, Anabela Ursino, Celeste Frascarolli, Alicia Amato, Rubén Dreszman, Juan Carlos Calvo, Judith Toneatto.
      Adipose tissue plays a crucial role in breast cancer (BC) progression by actively modulating the tumor microenvironment. We investigated how tumor proximity modifies adipose tissue by analyzing selected adipose-related and prognosis-associated markers in explants from BC patients and healthy donors. Explants were categorized by proximity to the tumor as adjacent (less than 2 cm), distant (over 2 cm), alongside normal explants (controls). FABP4 and vimentin expression was increased in proximity to the tumor, while caveolin-1, CD44, MMP9, and adiponectin showed minimal or no changes. Conditioned media (CM) from adjacent and normal explants were then assessed for their effects on tumorigenic traits in hormone-receptor-positive breast cancer (HR+ BC) and triple-negative breast cancer (TNBC) cell lines. Adjacent-CM enhanced migration, induced cytoskeletal remodeling, reduced adhesion, and promoted an elongated, motile phenotype in T47D cells. Poor-prognosis markers (caveolin-1, vimentin, CD44) were upregulated in at least one HR+ BC model, whereas Nanog and KLF4 showed modest variation. In TNBC cells, both normal- and adjacent-CM partially shifted MDA-MB-231 morphology toward a more epithelial-like state, decreasing caveolin-1 levels, while adjacent-CM increased MMP9 expression. Overall, these results reveal that adipose tissue-derived soluble factors exert significant and subtype-dependent effects on BC tumorigenicity.
    Keywords:  hormone receptors; human breast adipose tissue; tumor microenvironment; tumorigenesis
    DOI:  https://doi.org/10.3390/ijms27021129
  2. Int J Mol Sci. 2026 Jan 13. pii: 777. [Epub ahead of print]27(2):
    Inhibition of Breast Cancer Bone Metastasis by LRP5-Overexpressing Osteocytes via the LIMA1/MYO5B Signaling Axis.
    Yaning Chen, Zicheng Wang, Yu Sun, Xinshi Li, Yuji Wang, Shengzhi Liu.
      Bone metastasis in breast cancer remains a major therapeutic challenge because current osteoclast-targeted therapies do not fully disrupt the tumor-bone vicious cycle. Osteocytes, the most abundant bone cells, are increasingly recognized as key regulators of bone-tumor crosstalk. Previous work has shown that osteocyte-specific overexpression of the Wnt co-receptor LRP5 inhibits breast cancer-induced osteolysis and generates conditioned medium (CM) with tumor-suppressive activity. Proteomic analysis identified LIM domain and actin-binding protein 1 (LIMA1) as a central mediator that interacts with Myosin Vb (MYO5B), suggesting the role of the LIMA1/MYO5B regulatory axis. This study demonstrates that CM derived from LRP5-overexpressing osteocytes suppresses EO771 breast cancer cell proliferation, migration, and invasion, and downregulates tumor-promoting proteins, including MMP9, Snail, IL-6, and TGF-β1, while upregulating the apoptosis-related protein cleaved caspase-3. These effects were largely reversed by knockdown of LIMA1 or MYO5B. In syngeneic mouse models of mammary tumors and bone metastasis, systemic administration of LRP5-overexpressing osteocyte-derived CM reduced tumor burden and osteolytic bone destruction, whereas genetic knockdown of LIMA1 in osteocytes or MYO5B in tumor cells abrogated these protective effects. Collectively, these findings indicate that LRP5 activation in osteocytes engages the LIMA1/MYO5B signaling axis that inhibits breast cancer progression and osteolysis, disrupts tumor-stromal interactions, and restores bone-tumor homeostasis, thereby providing a potential therapeutic strategy to break the vicious cycle of bone metastasis in breast cancer.
    Keywords:  LIMA1; LRP5; MYO5B; bone metastasis; breast cancer; conditioned medium; osteocytes
    DOI:  https://doi.org/10.3390/ijms27020777
  3. Clin Breast Cancer. 2026 Jan 05. pii: S1526-8209(25)00356-8. [Epub ahead of print]
    LINC00511 Promotes Breast Cancer Cell Proliferation and Invasion by Mediating MYC-Mediated Regulation of VASP.
    Sirui Huang, Yiqing Xi, Jingbo Gao, Shilong Yu, Le Chen, Yuxia Duan, Zelin Yang, Yu Peng, Lei Wei, Jingwei Zhang.
       BACKGROUND: Breast cancer remains a significant health issue, with a persistent annual increase in incidence rates and high mortality. MYC, a critical transcription factor, is often dysregulated in breast cancer, driving tumor progression. Long noncoding RNAs (lncRNAs) have emerged as key regulators in cancer, influencing gene expression through various mechanisms. This study investigates the role of lncRNAs in mediating MYC function and their impact on breast cancer progression.
    METHODS: We analyzed 1212 breast cancer samples from The Cancer Genome Atlas (TCGA) database to identify lncRNAs related to MYC targets. The expression levels of lncRNAs were correlated with MYC-TARGET scores to develop a prognostic model. Functional studies were performed on LINC00511, a key lncRNA identified in the model, to elucidate its role in breast cancer progression. RNA Immunoprecipitation (RIP), Chromatin Immunoprecipitation (ChIP) and Dual-Luciferase Reporter Gene Assay assays were used to validate interactions between LINC00511, MYC, and the target gene VASP (vasodilator-stimulated phosphoprotein).
    RESULTS: MYC-TARGET scores were significantly correlated with poor prognosis in breast cancer patients. We identified 38 lncRNAs associated with MYC targets, and LINC00511 was selected for further analysis due to its high expression and correlation with poor prognosis. A prognostic model composed of 5 lncRNAs (including LINC00511) was developed, with a risk score that independently predicted patient outcomes . Functional experiments showed that LINC00511 promoted breast cancer cell proliferation, migration, and invasion. Mechanistically, LINC00511 interacted with MYC to upregulate VASP expression. VASP knockdown significantly reduced breast cancer cell proliferation and migration. Overexpression of MYC rescued the inhibitory effects of LINC00511 knockdown on VASP expression and cell invasion/migration.
    CONCLUSIONS: LINC00511 promotes breast cancer progression by mediating MYC to regulate VASP expression. This study highlights the importance of lncRNAs in cancer transcriptional networks and identifies LINC00511 as a potential therapeutic target for breast cancer.
    Keywords:  Prognostic model; Transcriptional regulation, lncRNA regulatory network, Tumor invasion and metastasis, Cell proliferation regulation
    DOI:  https://doi.org/10.1016/j.clbc.2025.12.010
  4. Cells. 2026 Jan 15. pii: 160. [Epub ahead of print]15(2):
    The WISP1/Src/MIF Axis Promotes the Malignant Phenotype of Non-Invasive MCF7 Breast Cancer Cells.
    Maria-Elpida Christopoulou, Panagiota Karamitsou, Alexios Aletras, Spyros S Skandalis.
      Breast cancer is a heterogeneous disease that exists in multiple subtypes, some of which still lack targeted and effective therapy. A major challenge is to unravel their underlying molecular mechanisms and bring to light novel therapeutic targets. In this study, we investigated the role of WNT-inducible signaling pathway protein 1 (WISP1) matricellular protein in the acquirement of an invasive phenotype by breast cancer cells. To this aim, we treated non-invasive MCF7 cells with WISP1 and assessed the expression levels of macrophage migration inhibitory factor (MIF) and its cellular receptor CD74. Next, we examined the expression of epithelial-to-mesenchymal transition (EMT) markers as well as molecular effectors of the tumor microenvironment, such as CD44, the main hyaluronan receptor that also acts as a co-receptor for MIF, the hyaluronan oncogenic network, and specific matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs). The results showed that WISP1 potently induces the expression of MIF cytokine and affects the expression of specific extracellular matrix molecules with established roles in the promotion of malignant properties. Notably, Src kinases and MIF are critically involved in these processes. Collectively, the present study demonstrates for first time a WISP1/Src/MIF axis as well as its ability to induce an invasive phenotype in MCF7 cells and highlights novel cellular and molecular processes involved in the epithelial-to-mesenchymal transition and the development of invasive breast cancer. This suggests that specific cues from the tumor microenvironment can activate a migratory/invasive phenotype in a subpopulation of cells residing within the heterogeneous breast tumor.
    Keywords:  CD44; MIF; MMPs; Src kinases; WISP1; breast cancer; hyaluronan
    DOI:  https://doi.org/10.3390/cells15020160
  5. Int J Biol Sci. 2026 ;22(3): 1520-1541
    The Interaction of CircESR1 and HNRNPAB Regulates Cell Cycle Transition of Breast Cancer Cell.
    Junchao Xu, Qiao Xu, Tingfang Cao, Miaomiao Wang, Yinzhong Shang, Junyan Tang, Sheng Wu, Xiaopeng Ma, Xinghua Han, Peter E Lobie, Liting Qian, Tao Zhu.
      The mechanisms by which circRNAs regulate estrogen receptor (ER)-positive breast progression and therapeutic resistance remain poorly defined. By screening circRNAs involved in ER signaling, circESR1 was identified as a novel circRNA exhibiting high specificity of expression in ER+ breast cancer. CircESR1 interacted with HNRNPAB, which was transcriptionally activated by ER/SP1 signaling. HNRNPAB promoted the back-splicing and expression of circESR1 by binding to the Alu elements of cognate pre-mRNA; and circESR1 transcripts increased the stability and expression of HNRNPAB, ensuring an efficient positive feedback loop as reflected in antiestrogen-resistant breast cancer cells. Furthermore, HNRNPAB interacted and stabilized CDK1 and CDK6 mRNA, which was facilitated by its asymmetrical binding of circESR1, to promote cell cycle progression. Patients whose cancer exhibited high levels of circESR1 and/or HNRNPAB exhibited advanced prognostic stage and poor survival. Combined use of circESR1 ASO and CDK4/6 inhibitors were shown to be an effective therapeutic approach overcoming antiestrogen resistance in breast cancer xenograft models. Hence, these findings elucidated a novel signaling complex centered around circESR1 and HNRNPAB in ER+ breast cancer, and suggested that circESR1 might represent a potential therapeutic target for this disease.
    Keywords:  HNRNPAB; breast cancer; cell cycle; circRNA; estrogen receptor; therapeutic resistance
    DOI:  https://doi.org/10.7150/ijbs.126014
  6. Cell Commun Signal. 2026 Jan 26.
    Exosome RAB10 inhibits JAK1/STAT1 to hinder macrophage M1 polarization and promote tumor immune escape.
    Tang Guohui, Pang Bo, Yuting Liu, Shaopeng Xu, Li Ruonan, Zhu Chengle, Wu Qiong, Ran Ruorong, Haotian Cai, Wang Wenrui, Chen Changjie, Yang Qingling.
      Exosomes are key mediators of communication between tumor cells and the tumor microenvironment(TME); however, the mechanisms underlying exosome-mediated crosstalk between tumor cells and macrophages remain largely unclear. This study investigated the effect of exosomal RAB10 on macrophage polarization and tumor growth. Mechanistically, RAB10 delivered by breast cancer cells binds to the interferon receptor IFNAR1 and inhibits JAK1/STAT1 pathway phosphorylation, thereby impeding M1 polarization and promoting M2 polarization. RAB10 expression was significantly upregulated in drug-resistant breast cancer cells and was correlated with poor patient prognosis. In vitro assays confirmed that RAB10 enhances cancer cell proliferation. In vivo knockdown of RAB10 suppressed tumor growth and reduced the expression of markers related to proliferation (Ki67, PCNA), invasion (MMP2), and epithelial-mesenchymal transition (Snail, Vimentin). Single-cell RNA sequencing revealed a marked decrease in the proportion of macrophages in the TME following RAB10 knockdown. This phenotypic shift increases the secretion of immunosuppressive factors such as PDL1, leading to reduced activity of CD8⁺ T cells. Animal studies further confirmed that combined targeting of RAB10 and PD-L1 produces a synergistic inhibitory effect on tumor growth. This study demonstrated that breast cancer cells can transfer RAB10 to macrophages via exosomes. RAB10 interacts with IFNAR1 to suppress the JAK1/STAT1 signaling pathway, thereby inhibiting M1 polarization and promoting M2 polarization of macrophages. Inhibition of RAB10, especially in combination with PD-L1 blockade, offers a promising strategy to enhance anti-tumor immunity and overcome therapeutic resistance in breast cancer.
    Keywords:  Breast cancer; Exosomes; Macrophage polarization; RAB10; scRNA-seq
    DOI:  https://doi.org/10.1186/s12964-026-02681-x
  7. PLoS One. 2026 ;21(1): e0341357
    RUBCN as a novel prognostic biomarker and therapeutic target in breast cancer.
    Dong Dong Yang, Cheng Hao Liu, Sheng Qiu Jia, Ze Kuan Xue, Ming Ming Zhang, Rui Yang, Yong Zhou Huang, Xin Chun Zhao, Bao San Han, Sheng Dong Nie, Gui Lin Huang, Ji Xue Hou.
      Analysis of autophagy-related gene expression data identified RUBCN as a novel biomarker influencing the pathogenesis and progression of breast cancer, underscoring its potential as a therapeutic target. We analyzed multiple breast cancer sample datasets using bioinformatics tools and databases. A consensus prognostic model was constructed and validated across several independent datasets to further examine its association with patient outcomes. A series of bioinformatics analyses focused on RUBCN were conducted, including expression profiling, independent prognostic evaluation, immune correlation analysis, and survival analysis. RUBCN expression was verified in breast cancer cell lines and clinical tissue specimens via Western blotting, quantitative real-time reverse transcription PCR, and immunohistochemistry. Functional assays, such as the Cell Counting Kit-8 assay, 5-ethynyl-2'-deoxyuridine incorporation assay, wound healing assay, and Transwell invasion assay, were employed to evaluate the effects of RUBCN knockdown on breast cancer cell proliferation and invasion. Autophagic activity, indicated by LC3 and P62 levels, was measured via Western blot in RUBCN-knockdown breast cancer cells with or without chloroquine treatment. Elevated expression of multiple autophagy-related genes was observed in breast cancer. The consensus prognostic model accurately predicted survival across multiple datasets, with RUBCN emerging as a key gene whose expression levels were significantly correlated with patient prognosis. Enrichment analysis indicated that RUBCN likely promotes breast cancer progression by regulating cell cycle and invasion processes. Further investigation revealed a negative correlation between RUBCN expression levels and immune cell infiltration, suggesting a potential role in mammary tumorigenesis through mediating immune evasion by suppressing immune cell infiltration. Immunohistochemical results confirmed upregulated RUBCN expression in carcinoma tissues. Knockdown of RUBCN was shown to suppress the proliferative and invasive abilities of breast cancer cells. Mechanistically, RUBCN knockdown impaired autophagic flux, as evidenced by altered LC3 and P62 levels upon chloroquine treatment. Together, these findings establish RUBCN as a promising therapeutic target in breast cancer. Future studies should emphasize in vivo functional validation using animal models and screen for targeted agents capable of modulating RUBCN expression or activity, thereby facilitating the development of innovative therapeutic strategies for breast cancer treatment.
    DOI:  https://doi.org/10.1371/journal.pone.0341357
  8. Curr Issues Mol Biol. 2025 Nov 24. pii: 974. [Epub ahead of print]47(12):
    USP30-AS1 Dictates Breast Cancer Cell Fate and Chemoresistance via a miR-3646/FZD7/Wnt/β-Catenin Circuit.
    Qian He, Shiyue Yang, Qilei Xin, Yapei Jiang, Li Jiang, Naihan Xu.
      Cancer stem cells (CSCs) play a pivotal role in promoting tumorigenesis, drug resistance, invasion, and metastasis. Recent studies indicate that long non-coding RNAs (LncRNAs) directly or indirectly regulate CSCs, influencing tumor progression. This study investigated the role of LncRNA USP30-AS1 in maintaining stemness and chemoresistance in breast cancer. USP30-AS1 was significantly upregulated in BCSC-enriched mammospheres derived from MDA-MB-231 and MCF-7 cell lines, where it correlated with elevated stemness markers (CD44, ALDH1A1, OCT4) and an increased proportion of ALDH+ cells. Functional experiments demonstrated that knockdown of USP30-AS1 reduced spheroid formation, stemness marker expression, chemoresistance, migration, and invasion, while its overexpression promoted these phenotypes. Mechanistically, USP30-AS1 acts as a competing endogenous RNA (ceRNA) by sponging miR-3646, which leads to the derepression of Frizzled-7 (FZD7) and subsequent activation of the Wnt/β-catenin signaling pathway. These findings identify USP30-AS1 as a critical promoter of stemness, chemoresistance, and metastasis in BCSCs via the miR-3646/FZD7/Wnt axis, suggesting it is a potential therapeutic target for breast cancer intervention.
    Keywords:  MicroRNA; WNT pathway; breast cancer; chemoresistance; long non-coding RNA; stem cells
    DOI:  https://doi.org/10.3390/cimb47120974
This page is being maintained by Thomas Krichel. It was last updated on 2026‒02‒08 at 0:21.