SLC3A2 (Solute Carrier Family 3 Member 2)

LRP8 facilitates CRC progression by antagonizing ferroptosis via modulation of the SLC3A2/GPX4 signalling axis. These findings highlight LRP8 as a previously unrecognized regulator of ferroptotic vulnerability and a potential therapeutic target in CRC.

Notably, glutamate depletion enhances the efficacy of neoadjuvant immunochemotherapy. Our findings provide insights into how the METTL3/m6A/CD98 axis-mediated regulation of glutamate efflux may sensitize HNSCC to neoadjuvant immunochemotherapy.

NRG1 fusions are oncogenic drivers in non-small cell lung cancer (NSCLC), with therapeutic relevance highlighted by the FDA's designation of Zenocutuzumab for NRG1 fusion-positive cases...No significant difference in progression-free survival was seen following first-line EGFR TKI therapy between uncommon and wild-type groups. Our findings highlight the heterogeneity of NRG1 fusions in NSCLC, revealing novel fusions, unique pathway enrichments, and expression profiles that may inform future personalized treatment strategies.

Additionally, Dau reduced tumor growth in vivo. Together, Dau enhanced ferroptosis and impeded neuroblastoma development by suppressing METTL1-mediated m7G methylation of SLC3A2, suggesting a novel therapeutic strategy for neuroblastoma.

These findings indicate that ferroptosis dysregulation is a hallmark of aggressive UM. SLC7A11, GPX4, and TFR1 represent clinically relevant biomarkers and potential therapeutic targets.

Herein, we analyze the LAT1/SLC7A5-mediated uptake of several essential AAs in FPR2-stimulated CaLu-6 and HCC1937 cells and prove: (i) the redox regulation of both LAT1/SLC7A5 and 4F2hc/SLC3A2/CD98, which form a heterodimer on the plasma membrane; (ii) the redox activation of the mTOR pathway and, in turn, of S6K1 and 4E-BP1, which stimulate protein synthesis; (iii) c-Myc and miR-126 regulation, which control LAT1/SLC7A5 synthesis at the transcriptional and post-transcriptional level, respectively. These findings provide new approaches for the development of novel therapeutic strategies for the treatment of human cancers.

Moreover, our data also establish that under low cell density conditions SLC1A5, SLC3A2, and AHR expression are under β-catenin and c-MYC control. As β-catenin promotes c-MYC gene induction, the current data allow us to propose that once cell-cell interaction is lost, the release of β-catenin from its interaction with cadherin triggers AHR activation and nuclear internalization.

Co-inhibition of mTOR or the SLC3A2/SLC7A5 complex using dactolisib or JPH203 restores sensitivity to KRAS inhibitors in vitro and in vivo. These findings support combinatorial targeting of mTOR signaling or amino acid transport to overcome intrinsic resistance in KRAS-mutant lung cancer.

Furthermore, Cy71-Ga NPs can disrupt glutathione synthesis and significantly enhance ferroptosis under laser irradiation. In general, this multimodal theranostic approach includes phototherapy, ferroptosis, chemotherapy of camptothecin, and immunotherapy, achieves an exceptional 83.85% tumor suppression rate in vivo and effectively prevents tumor metastasis.

According to in vivo experiments, UA inhibited CRC tumor growth by regulation of above genes. This study demonstrated that UA could effectively inhibit CRC proliferation by inducing ferroptosis via regulation of system xc- subunits and miR-214-3p/Stat3/GPX4 axis, suggesting UA could serve as a promising anti-colorectal cancer candidate requiring further validation and optimization.

The combination of ANPEP silencing and sorafenib treatment showed a synergistic effect in inhibiting liver cancer progression. Finally, clinical data and mouse models demonstrated that chronic stress drove liver tumor progression via ANPEP-regulated SLC3A2. These findings reveal unanticipated communication between chronic stress and metabolic reprogramming during liver cancer progression, providing potential therapeutic implications for liver cancer.

This new purification method results in LDN with high purity (more than 90%) and viability (more than 96%) in a short time period. This method can easily be scaled up to obtain large numbers of pure LDN to evaluate LDN functions in different diseases through biochemical or other omics analysis.