bims-meluca 2026-03-08 papers

J Cell Commun Signal. 2026 Mar;20(1): e70064

Phosphoenolpyruvate carboxykinase 2 activation of the AMPK-CEBPB axis to enhance glutamine utilization to promote glycolysis and malignant behavior in adenocarcinomas cells under glucose deprivation.

Libo Ruan, Kewang Xu, Wenjun Zeng, Ling Xiao, Minjun Zhao, Haiyan Zhang.

Glucose deprivation (Glu-D) is a critical feature of the tumor microenvironment. Under such conditions, tumor cells seek alternative metabolic resources to maintain rapid growth and proliferation. Glutamine serves as a key alternative resource for cancer cells, yet the metabolic mechanisms involving its transporters in non-small cell lung cancer remain poorly understood. Lentiviral vectors for overexpression and knockdown of phosphoenolpyruvate carboxykinase 2 (PCK2), solute carrier family 38 member 2 (SLC38A2), and CEBPB were constructed. Transwell, flow cytometry, Western blotting, and dual-luciferase reporter assays were used to investigate the regulatory relationship between PCK2 and SLC38A2 under Glu-D, as well as their effects on cellular glutamine metabolism, glycolysis, and malignant cell behaviors. PCK2 and SLC38A2 were highly expressed in human adenocarcinomas tissues. PCK2 upregulated SLC38A2 expression, though this effect was indirect. Under Glu-D, knockdown of PCK2 or SLC38A2 significantly reduced cellular glutamine utilization, inhibited glycolysis, and suppressed malignant cell behaviors. Treatment with an AMP-activated protein kinase (AMPK) inhibitor or knockdown of CEBPB produced similar effects. PCK2 activated AMPK, which increased downstream SLC38A2 expression by activating the transcription factor CEBPB. PCK2 upregulates SLC38A2 expression via the AMPK-CEBPB axis, enhancing glutamine utilization to promote glycolysis and malignant behaviors in A549 cells under Glu-D.

Keywords: AMPK‐CEBPB axis; NSCLC; PCK2; SLC38A2; glucose deprivation; glutamine utilization; metabolize

DOI: https://doi.org/10.1002/ccs3.70064

Oncology. 2026 Mar 02. 1-16

Weight variations during first-line systemic treatment of metastatic Non-Small Cell Lung Cancer: new paradigms from Real-World Data.

Alexandre Gravian, Arnaud Pagès, Anthony Tarabay, Virginie Delaye, Florian Scottée, Mansouria Merad, Sami Antoun.

Purpose In studies, weight loss is strongly associated with outcomes in metastatic non-squamous cell lung cancer (mNSCLC). This work examines weight variations in first-line treatment, exploring their mechanisms based on treatment type, age, sex, weight loss and excess weight before treatment. Methods A retrospective analysis was conducted on patients undergoing first-line treatment. Weight was recorded at four points: before treatment (Wbe), day one of treatment (Wd1), three months into immune checkpoint inhibitors (ICIs) treatment or maintenance (W3mo), and at progression diagnosis (Wpro). Results Among patients (n=198), 47% received chemotherapy (CT) with ICIs, 26% CT alone, and 27% ICIs alone. At Wd1, 32% were overweight/obese (Body mass index kg/m2) (BMI ≥25). Weight loss ≥ 5% before treatment was observed in 37%. Mean (SD) weight variations between Wd1 and W3mo were -1.1% (4.6) (CT), -0.2% (7.1) (CT+ICIs), and +0.4% (7.7) (ICIs alone) (P = 0.52). Patients older than 70 compared to ≤70 lost more weight between Wd1 and Wpro (-4.7% vs. -0.4%) (P = 0.019). Patients with pre-treatment weight loss ≥ 5% compared to those without weight loss stabilized or gained weight during treatment (+2.1% vs. -1.5%) (P = 0.009). Patients with BMI ≥25 lost more weight during treatment than those with BMI <25 (-1.4% vs. +0.8%) (P = 0.024). Conclusion Weight variations did not differ significantly across treatment types. Older patients are nutritionally more vulnerable. Pre-treatment significant weight loss ≥ 5% patients stabilized or gained weight during treatment, unlike those without initial weight loss. Pre-treatment weight loss in first-line mNSCLC supports, rather than contraindicates, cancer therapy. Higher BMI was associated with greater weight loss during treatment.

DOI: https://doi.org/10.1159/000550347

Biochim Biophys Acta Gen Subj. 2026 Mar 04. pii: S0304-4165(26)00025-5. [Epub ahead of print] 130925

Transcription factor FOSL2 enhances glycolytic metabolism and metastatic progression in lung adenocarcinoma via activation of BZW1.

Jiayan Fang, Yufeng Yang, Hongmin Cao, Dingke Chen, Xiaojia Zhu, Fei Wang.

As a pivotal mode of energy metabolism, glycolysis has been extensively validated for its role in facilitating diverse malignant phenotypes, most notably tumor proliferation and metastatic dissemination. This study aimed at exploring the role of BZW1 in lung adenocarcinoma (LUAD) glycolysis and metastasis. In our study, LUAD samples were collected and LUAD cell line (A549 and H1975) were employed. Gene expression was detected by quantitative real-time PCR, western blotting and immunohistochemistry. Cell migration and invasion were detected by wound healing and Transwell assay. Glycolysis level was analyzed by biomarker expression, lactate level detection, ECAR (extracellular acidification rate) experiment, intracellular ATP level and glucose consumption measure. The molecular interaction between FOSL2 and BZW1 was confirmed by dual-luciferase reporter assay, chromatin immunoprecipitation assay-qPCR (CHIP-qPCR) and electrophoretic mobility shift assay (EMSA). Our results showed that BZW1 was upregulated in LUAD tissues, compared with paracancerous tissues. Overexpressing BZW1 promoted metastatic behavior and glycolysis activity. Conversely, BZW1 knockdown had an opposite effect. Moreover, FOSL2 was identified as a transcriptional activator of BZW1. FOSL2 overexpression enhanced cell migration, invasion and glycolysis, which were reversed by BZW1 knockdown. BZW1 was also confirmed to promote LUAD progression in xenograft tumor model. In summary, our finding demonstrated that FOSL2 promoted glycolysis and metastatic potential in lung adenocarcinoma cells by transcriptionally activating BZW1, which provided a novel mechanism driving LUAD progression and suggested FOSL2-BZW1 signaling as a potential therapeutic target for LUAD.

Keywords: BZW1; FOSL2; Glycolysis; Lung adenocarcinoma; Metastasis

DOI: https://doi.org/10.1016/j.bbagen.2026.130925

PeerJ. 2026 ;14 e20866

Lactotransferrin upregulation affects the pathological changes of non-small cell lung cancer by regulating ferroptosis.

Yuxiu Wang, Wenjing Xu, Kaiqi Ren, Lingfeng Min.

Background: Recent studies have highlighted the role of ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, in cancer biology. This study aims to investigate the effect of lactotransferrin (LTF) upregulation on the pathological changes related to non-small cell lung cancer (NSCLC) via the inhibition of ferroptosis.
Methods: LTF's involvement in NSCLC was investigated through cell experiments and clinical samples. Cell models with stable LTF knockdown or overexpression were established by lentiviral transduction. Cell viability and cytotoxicity were evaluated through cell counting kit 8 (CCK8) and lactate dehydrogenase (LDH) experiments. Scratch and Transwell experiments were conducted to verify the effect of LTF expression on the migration and invasion abilities of lung cancer cells. Protein and mRNA expression were analyzed using Western blotting and qPCR. Malondialdehyde (MDA), glutathione (GSH), free iron ions (Fe2+), and reactive oxygen species (ROS) levels were measured with appropriate kits. The intracellular localization and expression of the protein was detected through immunofluorescence (IF). Peripheral blood of healthy controls and patients with preliminarily diagnosed non-small cell lung cancer was collected, and the expression levels of LTF protein and mRNA were detected by Western blotting and quantitative polymerase chain reaction (qPCR) experiments.
Results: The results demonstrate that LTF was upregulated in NSCLC and it's overexpression could significantly enhance the migration, invasion, and epithelial-mesenchymal transition (EMT) of non-small cell lung cancer cells. The overexpression of LTF significantly inhibited ferroptosis in non-small cell lung cancer cells. LTF modulates the expression of critical regulators of ferroptosis including glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long-chain family member 4 (ACSL4), leading to altered cellular redox status. The protein and mRNA expression levels of LTF were both increased in the peripheral blood of patients with NSCLC, with changes in protein level being more significant. Additionally, the overexpression of LTF was significantly correlated with the stage of NSCLC.
Conclusion: In conclusion, these findings suggest that LTF upregulation plays a crucial role in inhibiting ferroptosis, thereby influencing the pathological progression of NSCLC. This study provides a potential therapeutic avenue for targeting ferroptosis in NSCLC treatment strategies.

Keywords: Epithelial mesenchymal transformation (EMT); Ferroptosis; Lactotransferrin (LTF); Non-small cell lung cancer (NSCLC)

DOI: https://doi.org/10.7717/peerj.20866