GNG12 overexpression inhibits triple-negative breast cancer cell proliferation, migration, and invasion

Assessing the significance of CCNE1 overexpression in triple negative breast cancer.

TPD52 promotes breast cancer cell migration, invasion and proliferation via activation of the MAPK/ERK signaling pathway

Elevated TPD52 expression was associated with longer overall survival in specific subgroups, including the basal-like subtype, invasive lobular carcinoma, and N0/N1 stages, and a random forest-based diagnostic model demonstrated high accuracy across multiple datasets.

EI24 suppresses TNBC tumorigenesis by regulating AKT signaling

Introduction Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by limited targeted therapeutic options and frequent activation of the PI3K/AKT signaling pathway. EI24, a p53-responsive tumor suppressor involved in apoptosis, autophagy, and oncogenic signaling regulation, has been implicated in multiple cancer types; however, its functional role and molecular mechanism in TNBC remain incompletely understood. This study investigated the clinical relevance of EI24 in TNBC and examined its impact on AKT signaling and tumor progression. Methods Public breast cancer datasets and breast cancer patient samples were analyzed to assess EI24 expression patterns and clinical associations. Doxycycline-inducible EI24 overexpression systems were established in TNBC cell lines to evaluate cell proliferation and AKT pathway activity. Human phospho-kinase arrays, immunoblotting, co-immunoprecipitation, domain-mapping analyses, and immunofluorescence assays were performed to investigate the molecular mechanism underlying EI24-mediated AKT regulation. In vivo functional effects were examined using the MMTV-PyMT mammary tumor mouse model combined with mammary gland-specific Ei24 overexpression. Results EI24 expression was significantly reduced in TNBC patient samples and lower EI24 expression was associated with advanced tumor progression and poorer relapse-free survival. Inducible EI24 overexpression suppressed proliferation of TNBC cell lines and reduced AKT phosphorylation at both S473 and T308. In the MMTV-PyMT model, Ei24 overexpression inhibited mammary tumor growth, reduced pulmonary metastasis, and prolonged survival. Mechanistically, EI24 interacted with the pleckstrin-homology (PH) domain of AKT and impaired growth factor-induced AKT membrane translocation, suggesting that EI24 negatively regulates AKT activation by interfering with its spatial recruitment to the plasma membrane. Discussion These findings identify EI24 as a negative regulator of AKT signaling and support its tumor-suppressive role in TNBC progression. Our study provides mechanistic and in vivo evidence linking EI24 to AKT pathway regulation and supports further investigation of EI24-based approaches as potential therapeutic strategies for AKT-driven TNBC.

IFITM3 promotes triple-negative breast cancer progression by regulating β-catenin localization.

Interferon-induced transmembrane protein 3 (IFITM3) is best known as an antiviral protein, but accumulating evidence supports pro-tumorigenic functions across several cancers. Here, we examined IFITM3 in triple-negative breast cancer (TNBC). IFITM3 depletion suppressed MDA-MB-231 cell proliferation, migration, sphere formation, and xenograft tumor growth, whereas IFITM3 overexpression enhanced these phenotypes. IFITM3 depletion restored E-cadherin expression and increased membrane-associated E-cadherin-β-catenin complexes. These changes were accompanied by reduced nuclear active β-catenin and decreased Wnt/β-catenin transcriptional activity in cultured cells. Altered β-catenin localization was also observed in xenograft tumors. Conversely, IFITM3 overexpression enhanced WNT3a-responsive transcription and nuclear accumulation of active β-catenin. IFITM3 expression was elevated in breast tumors and was associated with shorter overall survival in a selected lymph-node-negative TNBC cohort. Together, these findings identify IFITM3 as a regulator of β-catenin localization and Wnt signaling that promotes epithelial-mesenchymal transition (EMT) and stem-like properties in TNBC cells.

EFO2 promotes triple-negative breast cancer progression and reduces CD8+ T cell-mediated killing by acetylating USF1 to enhance SLC2A1-mediated glycolysis.

Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by significant intratumoral heterogeneity and poor prognosis. Our study identified Establishment Factor-Like Protein 2 (EFO2) as a key oncogenic driver of TNBC progression. Using GEO datasets, we identified differentially expressed genes in TNBC. Functional roles of EFO2 were assessed via knockdown in human (MDA-MB-231, HCC1937) and mouse (4 T1, EMT6) TNBC cells, examining proliferation, glycolysis, and co-culture with CD8⁺ T cells. In vivo tumor growth was evaluated. Molecular mechanisms were investigated through co-immunoprecipitation, mutagenesis, luciferase reporter, and ChIP-qPCR assays. We observed that EFO2 was highly expressed in TNBC tissues, and this high expression correlated with shorter patient survival. Functional experiments showed that EFO2 knockdown suppressed tumor growth and proliferation both in vitro and in vivo. Furthermore, EFO2 knockdown inhibited glycolysis, as evidenced by decreased glucose uptake, ATP production, and lactate production. Moreover, EFO2 deficiency enhanced CD8⁺ T cell-mediated cytotoxicity against TNBC cells. Mechanistically, we demonstrated that EFO2 promoted the acetylation of Upstream Transcription Factor 1 (USF1), thereby enhancing transcriptional upregulation of the SLC2A1 promoter, a key glucose transporter. This EFO2/USF1/SLC2A1 signaling axis accelerated glycolysis in TNBC cells, which concurrently sustained tumor proliferation and impaired CD8⁺ T cell effector function, reducing TNBC cell susceptibility to T cell-mediated killing. Our findings identify a novel EFO2/USF1/SLC2A1 signaling axis that modulates glycolytic metabolism and CD8⁺T cell cytotoxicity, positioning EFO2 as a promising therapeutic target for TNBC treatment.

Functional Analysis of GAPDHP65 Suggests a Role in Triple-Negative Breast Cancer Viability 2257990

Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options. Dysregulated pseudogene expression is increasingly recognized in cancer progression, though many remain poorly characterized. This study examines GAPDHP65, a pseudogene involved in TNBC growth and survival. Computational analysis of gene expression profiles identified GAPDHP65 as highly expressed in TNBC compared to normal breast tissue. Experimental validation was conducted using the HCC-1937 TNBC cell line, where GAPDHP65 knockout was generated through CRISPR-Cas9 and editing efficiency was confirmed by indel detection and ligation sequencing. Cell viability and proliferation were measured in wild-type and knockout HCC-1937 cells using standard assays, forming the basis of our previously presented work. Current experiments are focused on expanding validation to the HTB-26 TNBC cell line and conducting detailed apoptosis and cell cycle analyses to further define GAPDHP65 function. GAPDHP65 expression was elevated in TNBC cells, and its knockout (validated by sequencing) reduced proliferation in HCC-1937 cells, suggesting a role in maintaining cell survival. Preliminary observations indicate similar trends in the HTB-26 line. Ongoing cell cycle and apoptosis analyses are aimed at determining whether GAPDHP65 loss alters S-phase progression or increases programmed cell death, which will further clarify its contribution to TNBC growth dynamics. Our previous work demonstrated that GAPDHP65 knockout impairs TNBC cell survival and progression, revealing its potential as a therapeutic target. These findings suggested that GAPDHP65 supports tumor growth by influencing apoptosis and cell cycle progression. Building on this foundation, the current study expands the analysis to additional TNBC lines and investigates downstream molecular changes following GAPDHP65 loss. n/a Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)