NDRG1 (N-Myc Downstream Regulated 1)

Human bronchial epithelial tumor cell (HBEC) lines H2030, H2030-BrM3, and H1299, with or without NDR2 depletion via siRNA or shRNA, were cultured for up to 24 h in the presence or absence of serum, and with or without the autophagosome-lysosome fusion inhibitor chloroquine (CQ)...Unlike NDR1, NDR2 is stabilized under starvation and promotes autophagy by regulating LC3 and ATG9A, thereby supporting NSCLC cell proliferation and migration. Routine staining for NDR2 and/or ATG9 could aid in diagnosing NSCLC with high migratory potential.

Drawing parallels with its dualistic role in tumor biology, we propose that NDRG1 acts as a dynamic integrator of environmental cues in the endothelium, orchestrating adaptive or maladaptive responses depending on microenvironmental context. These insights support a broader conceptual framework positioning NDRG1 as a potential biomarker and therapeutic target in cardiovascular disease.

Furthermore, MerTK or STK38 knockdown attenuated the activation of Rac1 and Cdc42. Taken together, these results revealed a novel role for STK38 in oncogenic Ras-induced enhanced cell migration, which may be useful for developing novel therapeutic strategies targeting Ras-mutated cells.

Considering expression frequency, specificity, and functional relevance, FTCD, GPD1, SOD2, and EIF4B Ser422 phosphorylation are further identified and validated as subtype prognostic biomarkers. This study provides critical insights into the molecular mechanisms underlying CRLM and offers resources for high-risk metastatic CRC.

Afatinib-resistant cell line (HCC827AR) was established by continuously exposing HCC827 cells to afatinib (4 µM) for 6 months...This study unravels the intricate role of NDRG1 in modulating NRG2 via HECW1. The results not only illuminate Mag's promising potential as an adjunctive therapy to surmount EGFR TKI resistance, but also underscore the significant therapeutic potential of targeting the NDRG1-NRG2-HECW1 pathway as a novel strategy to reverse EGFR TKI resistance in NSCLC.

Elevated IC50 values for oxaliplatin and 5-fluorouracil in metastatic samples were positively associated with NDRG1 and negatively with SRM, indicating chemo-resistance modulation. This five-gene epigenetic-transcriptomic hub identifies a molecular signature that warrants prospective validation as a potential biomarker for patient stratification and combination therapy in CRLM.

Risk model analysis predicted differential treatment responses: low-risk patients exhibited superior anti-PD-1 immunotherapy responses, whereas high-risk patients showed increased sensitivity to DNA-damaging agents (e.g., the Wee1 inhibitor MK-1775) and sorafenib. Plasma exosomal lncRNAs enable robust molecular subtyping, accurate prognostic stratification, and treatment response prediction in HCC. The ERG-centric classification system and validated 6-gene risk model provide clinically actionable tools for precision oncology.

Transcriptomic analysis identified a panel of immune-related genes (ADM, GHRH, SELENBP1, NDRG1) regulated by TSG-6. These findings indicate that ADSCs enhance graft tolerance by inhibiting DCs migration via TSG-6 secretion, highlighting TSG-6 as a promising therapeutic target for preventing transplant rejection.

In summary, this study revealed that NDR1 enhances the deubiquitination of AR mediated by USP9X, improving its stability and activity and thereby maintaining the continuous activation of the androgen signaling pathway in CRPC, leading to resistance to enzalutamide treatment. These findings suggest that cotargeting NDR1 and AR may represent a novel therapeutic strategy for AR-positive CRPC.

Moreover, treatment with a YAP inhibitor Verteporfin significantly attenuated the PPM1G-induced chemoresistance both in vitro and in vivo. Overall, our study elucidated a role of the PPM1G/NDR1/YAP axis in TNBC chemoresistance. We proposed that PPM1G may serve as a predictive biomarker for the treatment response of TNBC to YAP inhibitor.

The model also demonstrated associations with immune cell infiltration and drug sensitivity, highlighting its potential utility in optimizing immunotherapy and chemotherapy strategies. This study developed a novel ARG-based prognostic model that aids in survival prediction and therapeutic decision-making for metastatic melanoma patients. DOCK10 was identified as a potential therapeutic target in melanoma metastasis.