NCL (Nucleolin)

Conventional antibody-based modalities, including antibody-drug conjugates (e.g., sacituzumab govitecan against TROP2) and checkpoint inhibitors (e.g., atezolizumab for programmed death-ligand 1 [PD-L1]), leverage antibody-dependent cellular cytotoxicity, direct antigen blockade, and immune activation to combat tumor growth and evasion...Peptides, such as cell-penetrating variants and vaccines (e.g., HER2-derived AE37), disrupt oncogenic pathways, enable precise drug delivery via conjugates, and elicit antigen-specific immune responses. Aptamers provide high-affinity binding to antigens like nucleolin (e.g., AS1411), supporting targeted delivery and tumor microenvironment modulation. Together, these platforms hold strong potential to overcome chemoresistance, enable subtype-specific treatment personalization, and improve outcomes through synergistic combinations, advancing precision oncology in TNBC.

Overall, these findings suggest that LALBA and NCL are associated with tumor aggressiveness, immune context, and survival trends in breast cancer. Additional studies in larger cohorts are needed to define their clinical relevance.

These advancements directly overcome key limitations in enzymatic stochasticity and product heterogeneity through buffer engineering and computational optimization, establishing a scalable pathway for applications in precision nanomedicine, synthetic biology, and molecular data storage. This integrated strategy advances DNA nanotechnology from proof-of-concept studies toward standardized biomanufacturing of sequence-defined macromolecular architectures.

Thus, activated Ras can enhance the oncogenic effect of ErbB2 and NCL. These findings can be used to develop new ways to treat tumors that overexpress ErbB2/nucleolin and mutant Ras.

Finally, we review translational opportunities and challenges, including candidate biomarkers (tumor MDK by IHC/RNA and circulating MDK by ELISA) and rational combination strategies that pair MDK blockade with MAPK-pathway inhibitors or PD-1/PD-L1 immunotherapy. Collectively, these data position MDK as a tractable node connecting tumor-intrinsic signaling with stromal and immune regulation.

Moreover, NCL upregulation reversed miR-874-3p overexpression-mediated effects on the viability and proinflammatory cytokines in SGBS adipocytes. MiR-874-3p alleviates TNF-α-induced inflammatory response in SGBS adipocytes by downregulating NCL and inactivating NF-κB signaling.

We generated stable keratinocyte lines expressing doxycycline-inducible TurboID-tagged HPV16 E2 and confirmed that the tagged protein retained transcriptional, replicative, and DNA damage-inducing functions...Here, we define the E2 and TOPBP1 interactomes in differentiating keratinocytes and identify nucleolin (NCL) as a critical differentiation- and TOPBP1-dependent E2 partner required for episomal genome stability. These findings expand the understanding of how HPV16 coordinates viral replication with host chromatin and DNA repair networks, uncovering a cooperative E2-TOPBP1-NCL axis that may represent a new target for antiviral intervention.

AS1411 is a G-rich DNA aptamer that exhibits intrinsic antitumor activity through selective binding to nucleolin, a protein overexpressed in many cancers...One conjugate displayed an enhanced antiproliferative effect compared to the unconjugated components, underscoring the therapeutic potential of this modular design. Overall, this work demonstrates the potential of aptamer-peptide conjugates as a promising strategy for next-generation targeted cancer therapeutics, combining targeted delivery with synergistic therapeutic effects.

This aptamer was conjugated to the nucleolin-targeting aptamer AS1411, generating a single-strand PROTAC (AP-SETDB1-S6A) and a partial double-strand PROTAC (AP-SETDB1-D2), both of which exhibit good serum stability...Functional assays demonstrated that both AP-SETDB1-S6A and AP-SETDB1-D2 significantly inhibit breast cancer cell proliferation and migration, and resensitize drug-resistant breast cancer cells to tamoxifen. Notably, they further enhance the cytotoxic activity of CD8+ T cells against breast cancer cells and directly target breast cancer cells to suppress tumor growth in vivo. This study establishes dual aptamers-based PROTACs targeting SETDB1, offering effective therapeutic strategies for breast cancer treatment.

This study provides compelling evidence demonstrating that C4 is a highly promising anticancer compound. It also provides important evidence for the development of novel nucleic acid aptamer-PROTAC conjugate drugs for more clinical applications.

Our in vivo data demonstrate that SLU7 is a promising, versatile target for possibly diverse cancers. Its multimodal mechanism offers potential to overcome tumor heterogeneity, reverse immune tolerance, and enhance immunotherapy efficacy.

Furthermore, all models demonstrated key properties of cancer stem cells, although with varying degrees of expression of progenitor and stem cell markers, which could be dynamically modulated by treatments and therapies. Overall, our results draw parallels between canonical and noncanonical Wnt signaling, differential cytoskeletal remodeling, stemness properties and various cellular plasticities in primary tumor and metastasis-derived models of ACC.