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Background Glutamine is an abundant and versatile nutrient in cancer cells. Head and neck squamous cell carcinoma (HNSCC) was reported to be dependent on mainly glucose, not glutamine, for producing the energy required for survival and proliferation. Methods The roles of ASCT2 (SLC1A5) and associated glutamine metabolism were determined by the MTT, colony formation, glutamine uptake, intracellular glutathione, ROS detection, immunofluorescence, immunohistochemistry, and apoptosis enzyme-linked immunosorbent assays as well as animal studies. Results We found that glutamine is also critical for HNSCC. In this study, ASCT2, an amino acid transporter responsible for glutamine transport, in addition to LAT1 and GLS, is overexpressed in HNSCC and associated with poor survival. Using both in vivo and in vitro models, we found that knocking down ASCT2 by shRNAs or miR-137 or the combination of silencing ASCT2 and pharmacologically inhibiting SNAT2 via a small-molecule antagonist called V-9302 significantly suppressed intracellular glutamine levels and downstream glutamine metabolism, including glutathione production; these effects attenuated growth and proliferation, increased apoptosis and autophagy, and increased oxidative stress and mTORC1 pathway suppression in HNSCC. Additionally, silencing ASCT2 improved the response to cetuximab in HNSCC. Conclusions In summary, ASCT2-dependent glutamine uptake and subsequent glutamine metabolism are essential for HNSCC tumorigenesis, and the combination of glutamine uptake inhibitors and cetuximab presents a promising strategy for improving the outcomes of HNSCC patients.

People tend to obtain information through fragmented reading. However, this behavior itself might lead to distraction and affect cognitive ability. To address it, it is necessary to understand how fragmented reading behavior influences readers’ attention switching. In this study, the researchers first collected online news that had 6 theme words and 60 sentences to compose the experimental material, then defined the degree of text dissimilarity, used to measure the degree of attention switching based on the differences in text content, and conducted an EEG experiment based on P200. The results showed that even after reading the fragmented text content with the same overall content, people in subsequent cognitive tasks had more working memory capacity, lower working memory load, and less negative impact on cognitive ability with the text content with lower text dissimilarity. Additionally, attention switching caused by differences in concept or working memory representation of text content might be the key factor affecting cognitive ability in fragmented reading behavior. The findings disclosed the relation between cognitive ability and fragmented reading and attention switching, opening a new perspective on the method of text dissimilarity. This study provides some references on how to reduce the negative impact of fragmented reading on cognitive ability on new media platforms.

The actin cytoskeletal architecture provides the structural underpinnings for crucial cellular behaviors. In cancer cells, changes in the actin cytoskeleton may serve as prerequisites for proliferation, invasion, and metastatic dissemination. However, the underlying mechanisms remain largely unknown. Here, we show that MICAL2, which is increased in head and neck squamous cell carcinoma (HNSCC) and inversely associated with patient survival, promotes HNSCC growth, invasion, and migration. MICAL2 serves as a flavoprotein monooxygenase and directly induces actin filament depolymerization by specifically oxidizing the methionine 44 and 47 residues of F-actin. The kinase ARG interacts with MICAL2 and augments MICAL2-mediated actin disassembly. Direct phosphorylation assay and mass spectrometry confirmed that ARG phosphorylates MICAL2 at Tyr445, Tyr463, and Tyr488. Substitution of the Tyr445 or Tyr463 residue of purified recombinant MICAL2-redox with phenylalanine (generating a non-phosphorylatable mutant) abolishes the enhanced MICAL2-mediated F-actin disassembly induced by ARG. Consistently, ectopic expression of non-phosphorylatable MICAL2 mutants (MICAL2 Y445F and MICAL2 Y463F , not MICAL2 Y488F ) failed to ameliorate HNSCC cell growth, whereas expression of wild-type MICAL2 or MICAL2 Y488F rescued the impaired proliferation induced by MICAL2 knockdown. Moreover, CCG-1423, an inhibitor of MICAL2, was shown to inhibit HNSCC cell proliferation, invasion, and migration. Taken together, our findings indicate that phosphorylation of MICAL2 at Tyr445 and Tyr463 by ARG mediates F-actin disassembly and promotes HNSCC progression.

Cancer cells and the nervous system engage in a dynamic interplay, significantly influencing initiation and progression in head and neck squamous cell carcinoma (HNSCC). Our findings highlight that cancer cells drive an increase in caveolin-2 (Cav2) expression within trigeminal ganglia and associated neural fibers in the tumor milieu, fostering a reciprocal attractant relationship between tumor cells and nerves. Notably, the knockout of Cav2, either globally or specifically in sensory neurons or glial cells, markedly attenuates the growth of orthotopically implanted tongue tumors. Moreover, Cav2-expressing nerves are implicated in shifting cancer cell metabolism towards mitochondrial oxidative phosphorylation, a process involved in maintenance of cancer stem cells (CSCs). Our results also demonstrate that Cav2-expressing nerves confer stemness properties to cancer cells. Disruption of Cav2 expression, both globally and in specific neural cell types, impedes tumorigenesis and progression in a 4-NQO-induced HNSCC mouse model. This interplay observed between cancer cells, neurons, and glial cells suggests a potential mechanism through which tumor-associated nerves might influence cancer stemness via metabolic reprogramming. This highlights a possible direction for anticancer therapy that warrants further investigation. The peripheral nervous system plays a role in the development of head and neck squamous cell carcinoma (HNSCC). Here the authors show that HNSCC cancer cells promote the expression of caveolin-2 (Cav2) on neural cells, while Cav2-expressing neurons or glial cells induce a mitochondrial oxidative phosphorylation phenotype in cancer cells to maintain cancer stemness.

Background Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer with alarmingly high morbidity. The cancer-associated fibroblasts (CAFs) play a pivotal role in tumor development, while their specific mechanisms in OSCC remains largely unclear. Our object is to explore a CAFs-related biomarker in OSCC. Methods Single-cell RNA sequencing (ScRNA-seq) analysis was used to pinpoint CAF clusters in OSCC samples. Differentially expressed genes and Cox regression analyses were used to identify candidate genes, and their functions were evaluated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The prognostic performance of the identified biomarker was evaluated using receiver operating characteristic analysis. The qPCR and western blot were used to assess gene expression. The hub gene related immune characteristics were analyzed in independent cohorts, and gene expression differences between different immunotherapy response groups were investigated using Pearson correlation analysis. Results Desmoglein-2 ( DSG2 ) was identified as a CAFs-related biomarker in OSCC exhibiting elevated expression compared to controls and being associated with poor prognosis. Enrichment analyses revealed that DSG2 was involved in signal transduction pathways like focal adhesion. The Area Under Curve values of DSG2 in predicting prognosis exceeded 0.6 in both training-set and validation-set. Furthermore, patients with low DSG2 expression were more likely to benefit from immunotherapy than those DSG2 highly expressed patients. Conclusion Our study identified DSG2 as a reliable CAFs-related prognostic biomarker in OSCC, providing a new reference for the mechanistic understanding and target therapy of this malignancy.

Breast cancer anti-estrogen resistance protein 3 (BCAR3) is involved in anti-estrogen resistance and other important aspects of breast cancer. However, the role of BCAR3 in other solid tumors remains unclear. The relationship between the clinicopathologic characteristics of head and neck squamous cell carcinoma (HNSCC) patients and BCAR3 was analyzed using the Wilcoxon’s signed-rank test and logistic regression. The association between BCAR3 expression and clinicopathologic features and survival was analyzed using Cox regression and the Kaplan–Meier method. In vivo and in vitro assays were performed to validate the effect of BCAR3 on HNSCC growth. BCAR3-related mRNAs were determined by calculating the Pearson’s correlation coefficient based on The Cancer Genome Atlas (TCGA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and gene set enrichment analysis (GSEA) were used to predict the potential functions of BCAR3. BCAR3 expression is overexpressed in HNSCC and was shown to be associated with perineural invasion (PNI) and poor survival. BCAR3 silencing significantly attenuated the proliferation of HNSCC cells, whereas BCAR3 depletion inhibited tumor growth in vitro. GO and KEGG functional enrichment analyses, and GSEA showed that BCAR3 expression in HNSCC was associated with biological processes, such as cell adhesion, actin binding, cadherin binding, and angiogenesis. BCAR3, which promotes HNSCC growth, is associated with perineural invasion and may be a potential molecular prognostic marker of poor survival in HNSCC.

More than half of HNSCC patients are diagnosed with advanced disease. Locally advanced HNSCC is characterized by tumors with marked local invasion and evidence of metastasis to regional lymph nodes. CAV2 is a major coat protein of caveolins, important components of the plasma membrane. In this study, CAV2 was found to profoundly promote invasion and stimulate metastasis in vivo and in vitro. CAV2 was demonstrated to be a key regulator of S100 protein expression that upregulates the proteins levels of S100s, which promotes the invasion and migration and downregulates the expression of tumor suppressors. Mechanistically, CAV2 directly interacts with S100s in HNSCC cells, and CAV2 reduces S100A14 protein expression by promoting its ubiquitylation and subsequent degradation via the proteasome. Moreover, we discovered that CAV2 promotes the interaction between S100A14 and the E3 ubiquitin ligase TRIM29 and increases TRIM29 expression. Taken together, our findings indicate that CAV2 promotes HNSCC invasion and metastasis by regulating the expression of S100 proteins, presenting a novel potential target for anticancer therapy in HNSCC.

Traffic sensing system requires to periodically collect spatial–temporal traffic data distributed among road networks, which results in overhigh bandwidth consumption and storage cost in a large-scale road network. Several compressive sensing-based algorithms are proposed to reconstruct missing traffic data with limited traffic observation. However, there still exist great challenges to be addressed. First, these existing algorithms are always iteration-based, whose time complexity will explosively increase with the growth of network scale. Furthermore, these algorithms have to be re-executed even if only a small fraction of data changes, which is not suitable for dynamic traffic environments. To overcome these issues, we investigate a novel service architecture of traffic sensing based on mobile edge computing where collected data is pre-processed at the edge node and reconstructed at cloud servers, respectively. On this basis, we formulate the problem of Missing Traffic Data reconstruction (MTDR), which aims at maximizing data reconstruction accuracy within limited observation data. Further, we develop a deep-learning-based algorithm called stacked denoising autoencoder for MTDR (SDAE-MTDR), where three denoising autoencoders are trained in order and then stacked together for parameter fine-tuning based on cross-entropy-based loss function. Finally, we conduct comprehensive performance evaluation based on realistic vehicular traces and the simulation results demonstrate the superiority of the proposed algorithm compared with competitive solutions.

Background Anaplastic thyroid cancer (ATC) is the greatest lethal thyroid neoplasm with a low incidence and lacks an effective treatment strategy and standardized treatment protocol. PLX3397 (Pexidartinib) is an FDA-approved multitarget tyrosine kinase inhibitor. The research is designed to explore the possible anti-proliferative activity of pexidartinib on ATC, as well as its related molecular mechanisms. Methods The cell viability was assessed by CCK-8, LDH release, colony formation, and EdU detection assays. Apoptosis and the alteration on cell cycle arrest were characterized by flow cytometry (FCM). ER stress was evaluated by immunofluorescence (IF). ROS levels were determined by flow cytometry. Western blot assays were conducted to evaluate changes in key molecules related to apoptosis and ER stress. The ATC xenografts model was established, and immunohistochemistry was performed to validate the anti-ATC effects of pexidartinib in vivo. Results Pexidartinib significantly inhibited ATC cell proliferation and induced apoptosis and cell cycle arrest. Moreover, pexidartinib potently induced ER stress and elevated ROS in ATC cells, and the apoptotic cells and ER stress in ATC after administration of pexidartinib could be reversed by an ER stress inhibitor and ROS scavenger, respectively. Furthermore, pexidartinib treatment induced Nrf2 accumulation in nuclei and reduced the interaction of Nrf2 with Keap-1, and knockdown of Nrf2 enhanced the anti-ATC effects of pexidartinib in vitro. In addition, pexidartinib significantly inhibited ATC xenograft growth and proliferation in vivo, and the combination of ML385, an Nrf2 inhibitor, potently enhanced the anti-ATC effects of pexidartinib in vivo. Conclusion Our findings suggest pexidartinib is a potential agent for treating ATC. Co-administration with an Nrf2 inhibitor is an effective synergistic strategy.

Anaplastic thyroid cancer (ATC) is the highest lethal type of thyroid cancer. Regrettably, ATC patients respond poorly to multiple treatment strategies. Therefore, there is imperative to strengthen the therapeutic approach to this vicious form of cancer. In the present study, we found that pexidartinib induces ER stress and elevated ROS in ATC cells. The apoptotic cells, and ER stress in ATC after administration of pexidartinib could be reversed by ER stress inhibitor and ROS scavenger, respectively. Furthermore, pexidartinib treatment induced Nrf2 (Nuclear Factor Erythroid 2-related Factor 2) accumulation in nuclei and reduced the interaction of Nrf2 with Keap-1 (Kelch-like ECH-associated protein 1), while the knockdown of Nrf2 enhanced the anti-ATC effects of pexidartinib in vitro. In addition, pexidartinib significantly inhibits ATC xenografts growth and proliferation in vivo, and the combination of ML385, an Nrf2 inhibitor, potently enhanced the anti-ATC effects of pexidartinib in vivo. Our findings suggest pexidartinib to be a potential agent for treating of ATC. Background Anaplastic thyroid cancer (ATC) is the greatest lethal thyroid neoplasm with a low incidence and lacks an effective treatment strategy and standardized treatment protocol. PLX3397 (Pexidartinib) is an FDA-approved multitarget tyrosine kinase inhibitor. The research is designed to explore the possible anti-proliferative activity of pexidartinib on ATC, as well as its related molecular mechanisms. Methods The cell viability was assessed by CCK-8, LDH release, colony formation, and EdU detection assays. Apoptosis and the alteration on cell cycle arrest were characterized by flow cytometry (FCM). ER stress was evaluated by immunofluorescence (IF). ROS levels were determined by flow cytometry. Western blot assays were conducted to evaluate changes in key molecules related to apoptosis and ER stress. The ATC xenografts model was established, and immunohistochemistry was performed to validate the anti-ATC effects of pexidartinib in vivo. Results Pexidartinib significantly inhibited ATC cell proliferation and induced apoptosis and cell cycle arrest. Moreover, pexidartinib potently induced ER stress and elevated ROS in ATC cells, and the apoptotic cells and ER stress in ATC after administration of pexidartinib could be reversed by an ER stress inhibitor and ROS scavenger, respectively. Furthermore, pexidartinib treatment induced Nrf2 accumulation in nuclei and reduced the interaction of Nrf2 with Keap-1, and knockdown of Nrf2 enhanced the anti-ATC effects of pexidartinib in vitro. In addition, pexidartinib significantly inhibited ATC xenograft growth and proliferation in vivo, and the combination of ML385, an Nrf2 inhibitor, potently enhanced the anti-ATC effects of pexidartinib in vivo. Conclusion Our findings suggest pexidartinib is a potential agent for treating ATC. Co-administration with an Nrf2 inhibitor is an effective synergistic strategy.