SLC3A2 expression

Immunohistochemistry showed HMGB3 expression correlated with ferroptosis-associated proteins and IRF1 expression in breast cancer tissue. HMGB3 contributes to anti-PD-1 resistance by inhibiting IFN-γ-driven ferroptosis in TNBC which suggested HMGB3 is a potential co-target with anti-PD-1 therapy for TNBC.

SLC3A2 expression was further confirmed via qRT-PCR. The impact of SLC3A2 on EC's malignant behavior was corroborated through both in vitro and in vivo experiments.

Then, the PPARγ inhibitor (GW9662), autophagy inhibitor (3-MA) and autophagy inducer (rapamycin; Rap) were used to further study the potential mechanism of YHD on TNBC...3-MA had the similar effects to GW9662. Collectively, YHD suppressed the malignant progression of MDA-MB-231 cells by inducing ferroptosis through PPARγ-dependent autophagy.

NPB15 injection showed antitumor activity in an HCC xenograft mouse model. The results suggest that NPB15 may be developed as a therapeutic antibody for HCC patients.

Moreover, inhibiting both USP1 and EV secretion synergistically enhanced the cytotoxicity of PEG-asp. These data suggest that targeting CD98hc in the treatment of ENKTL may be beneficial in overcoming drug resistance.

Moreover, the ANO6-plasmid inhibited GIST growth in vivo. Therefore, ANO6 may be a promising therapeutic target for blocking the development of GIST via the induction of apoptosis, pyroptosis, and ferroptosis.

Moreover, EMPA suppressed bioluminescence of 4T1-Red-FLuc induced thoracic cavity, peritoneal tumour burden and lung nodules in an in vivo metastatic model of breast cancer. Collectively, we revealed that EMPA sensitized the ECM detached cells to ferroptosis by synergically activating miR-128-3p and lowering the levels of SP1 and CD98hc, making it a potential adjunct drug for breast cancer chemotherapy.

The compound demonstrated potent antitumor effects derived from MMAE against SLC3A2-expressing HNSCC in preclinical models, displaying a favorable safety profile. These findings suggest that targeting SLC3A2 with an anti-SLC3A2 ADC could be a promising therapeutic approach for treating HNSCC patients.

In colorectal cancer, CD98hc emerges as a potential therapeutic target, along with its partner LAT1, and inhibitors like JPH203 exhibit promise in preclinical studies. Targeting CD98hc/LAT1, alone or with conventional therapies, shows promise in inhibiting tumor growth. This review focuses on elucidating the multifaceted roles of CD98hc and its partner LAT1 in cancer, particularly its involvement in amino acid transport, signaling pathways, and its prognostic relevance in cancer.

However, the impact of SLC3A2 interference on cell proliferation and macrophage polarization was impeded by ferroptosis inhibitors. Interference with SLC3A2 inhibited the growth of BLCA cells and the polarization of tumor-associated macrophages by promoting ferroptosis in BLCA cells.

Our results show that: (1) In glucose presence, μ increased, but qS Glucose and qP Lactate decreased when tumor cells were cultured under acidosis as opposed to neutral conditions; (2) most lung cancer cell lines consumed lactate under normoxia or hypoxia; (3) although qS Glutamine diminished under hypoxia or acidosis, it slightly increased in lactate presence, a finding that was associated with CD98 upregulation; and (4) under acidosis, G0/G1 arrest was induced in A427 cancer cells, although this phenomenon was significantly increased when glucose was changed by lactate as the predominant carbon-source. Hence, our results provide an understanding of metabolic responses that tumor cells develop to survive under stressful conditions, providing clues for developing promising opportunities to improve traditional cancer therapies.

Furthermore, in combination with ferroptosis agonist metformin, short-term acidosis could synergistically inhibit viability and enhance the ferroptosis of BC cells. Meanwhile, by the exploration of immune cells, short-term acidosis also induced M1 macrophage polarization, triggering processes of phagocytosis and ferroptosis in BC cells. This study demonstrated that short-term acidosis induced BC cell ferroptosis through ZFAND5/SLC3A2 signaling axis and promoted phagocytosis and ferroptosis of BC cells with M1 macrophage polarization, which might be a new mechanism for BC therapy.

Oral administration of LNPs mitigated UC and CAC by alleviating inflammation, restoring the colonic barrier, and modulating intestinal microbiota. As the first oral CRISPR/Cas9 delivery LNP, this system offers a precise and efficient platform for the oral treatment of colon diseases.

Taken together, knockdown of hsa_circ_0050900 inhibited SLC3A2 expression via sponging hsa-miR-605-3p to promote ICC cell ferroptosis, and finally suppressed proliferation and migration. The present study suggested that hsa_circ_0050900 was a potential therapeutic target for ICC.

Reduced SLC3A2 expression in OSCC promotes immune evasion and tumour progression by impairing T lymphocyte function. This study provides insights into targeted regulation of SLC3A2 expression for immune response-based therapies in OSCC.

System Xc overexpression compromised the metabolic flexibility of OSCC under GD conditions, and thus, glucose starvation therapy is effective for killing OSCC cells.

A high expression of CD98hc has been linked to clinical prognosis and response to chemo- and radiotherapy in several types of cancer. In this mini-review, we discuss the physiological functions of CD98hc, its role in regulating tumor stemness, metastases, and therapy resistance, and the clinical significance of CD98hc as a tumor marker and therapeutic target.

The treatment options were radiation therapy with either cisplatin or cetuximab, and surgery. Via CD98 immunostaining, sensitivity to radiotherapy can be determined in advance. In HNSCC, knowledge about sensitivity to radiotherapy can significantly improve prognosis.

The main finding of this study is that ALDH2 inhibited BSG expression through the TGF-β1 pathway, which indirectly inhibited SLC3A2 expression; subsequently, the sphingolipid metabolism pathway was also inhibited in HCC cells. Therefore, SLC3A2 is a novel target for HCC treatment.

In vitro fermentation system confirms the metabolic cross-feeding of C. maltaromaticum with Faecalibacterium prausnitzii to convert C. maltaromaticum-produced 7-dehydrocholesterol into vitamin D for activating the host VDR signaling. Overall, C. maltaromaticum colonizes the gut in an estrogen-dependent manner and acts along with other microbes to augment the intestinal vitamin D production to activate the host VDR for suppressing CRC.

The studies herewith reported indicate that CD98hc may represent a novel ADC target that, upon well-designed clinical trials, could be used to increase the therapeutic armamentarium against CRC.

Noteworthily, everolimus (a targeted therapy drug for BC) related protein, FK506-binding protein 1A (FKBP1A) was found to bind with SLC3A2, and negatively regulated SLC3A2 expression during the processes of everolimus inducing ferroptosis of BC cells and promoting anti-proliferation of Th9 lymphocytes. Altogether, our study strongly implies that SLC3A2 is an immuno-oncogenic factor and FKBP1A/SLC3A2 axis would provide insights for a novel immunotherapy approach for the treatment of BC in the context of TME.

CAR-T cells specific for activated integrins, which are consistently overexpressed in multiple myeloma, are one of the achievements. We recently discovered an antibody with myeloma specificity despite binding to a ubiquitously expressed protein, CD98hc, and hypothesized that this specificity may be owing to altered N-glycosylation of CD98hc.

CD147 and CD98hc were correlated with DNA repair, the cell cycle, and DNA replication. The CD98hc-CD147 complex could serve as a target for ovarian cancer treatment.

More importantly, we demonstrated that arachidonic acid was responsible for SLC3A2 mediated macrophage polarization in the tumor microenvironment to differentiate into M2 type both in vitro and in vivo. Our data illustrate previously undescribed mechanisms responsible for TAMs polarization and suggest that SLC3A2 acts as a metabolic switch on lung adenocarcinoma cells to induce macrophage phenotypic reprogramming via arachidonic acid.

TEAD1 confers resistance of HCC cells to ferroptosis, thereby promoting the progression of HCC, suggesting the potential value of TEAD1 in the diagnosis and treatment of HCC.

Background: Up to 40% of diffuse large B-cell lymphoma (DLBCL) patients do not achieve a cure in response to standard immunochemotherapy R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)...To further explore the role of the CD98hc counteracting mechanism, we established a doxycycline-inducible (TET-on) CD98hc-overexpressing DLBCL cell line (SU-DHL10), and we consistently found that overexpression of CD98hc was responsible for decreased sensitivity to zotatifin treatment (48h, 72h) by ATP-dependent viability assay... We define for the first time CD98hc as a new putative driver of rocaglate resistance in B-cell lymphoma. Paradoxically, CD98hc is upregulated as part of an overall cellular translational response to rocaglate exposure, but it provides insights and new potential targets for further drug combinations. This study lays the foundation for new treatment strategies to optimize the use of zotatifin to overcome rocaglate resistance in lymphoma patients.

Addition of essential amino acids or expression of 4F2 (SLC3A2) partially restored growth following loss of GCN2, suggesting that GCN2 targeting of SLC transporters is required for amino acid homeostasis needed to sustain tumor growth. A small molecule inhibitor of GCN2 showed robust in vivo efficacy in androgen-sensitive and castration-resistant mouse models of PCa, supporting its therapeutic potential for the treatment of PCa.

Few molecular mechanisms by which SLC3A2 regulates anti-tumor immunity have been clarified in the present study, which is the main limitation. Future research into the biological mechanism could further help with targeted treatment for cancer patients.

SLC7A5, SLC7A8, SLC38A1, and SLC38A2 may regulate the polarization of tumor-associated macrophages (TAMs). SLC1A5, SLC3A2, SLC7A5, and SLC6A14 may be promising biomarkers for the BC diagnosis and may represent potential therapeutic targets for these patients.

The Akt/GSK-3β pathway was found to participate in regulating MIF and SLC3A2 both in vivo and in vitro. MIF and SLC3A2 might be potential biomarkers for monitoring the treatment of colorectal cancer.

Our results indicate that select amino acid limitations activate GCN2 in PCa, resulting in the upregulation of key amino acid transporters, including 4F2 (SLC3A2), which provide for nutrient import to facilitate protein synthesis and metabolism required for PCa progression. We conclude that GCN2 and the ISR are promising therapeutic targets for both androgen-sensitive and castration-resistant prostate cancer.

Our findings indicated that miR-142-3p promoted HBV-infected M1-type macrophage ferroptosis through SLC3A2, affecting the production of GSH, MDA, and Fe and accelerating the development of HCC. The regulation of miR-142-3p and its target genes will help to clarify the pathogenesis of HCC induced by HBV infection and provide new theoretical foundations and therapeutic targets.

CD98hc is expressed in a remarkable percentage of pancreatic ductal adenocarcinomas. Due to its important role in cell behavior and malignant cell transformation, it may be a promising molecular target for potential new therapeutic approaches in pancreatic cancer in the future.

Three biomarker signatures were defined for patients with locally advanced HNSCC treated with primary RCTx for the endpoints LRC and OS. These signatures will be validated in the prospective HNprädBio study of the DKTK-ROG that recently completed recruitment, before potential application in an interventional trial.

Our study revealed that CD98hc was a marker of cells originated from basal cell in esophagus, ectopic expression of CD98hc in hyperplastic/dysplastic cells by chronic inflammation stimulation crippled the linkage between basal cell and basement membrane, sabotaged the integrity of the barrier in between lamina propria and epithelium, subsequentially initiate carcinogenesis.

Our study suggests that SLC3A2 negatively regulates ferroptosis through mTOR pathway in laryngeal carcinoma.

CD98hc expression decreased while metastasizing to regional lymph nodes. However, CD98hc and LAT1 expressions had no prognostic value in patients with CRC.