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Aberrant activation of Wnt/β-catenin signaling and dysregulation of metabolism have been frequently observed in lung cancer. However, the molecular mechanism by which Wnt/β-catenin signaling is regulated and the link between Wnt/β-catenin signaling and cancer metabolism are not fully understood. In this study, we showed that the loss of dual serine/threonine tyrosine protein kinase (DSTYK) led to the activation of Wnt/β-catenin signaling and upregulation of its target gene, lactate dehydrogenase (LDHA), and thus the elevation of lactate. DSTYK phosphorylated the N-terminal domain of β-catenin and inhibited Wnt/β-catenin signaling, which led to the inhibition of cell growth, colony formation and tumorigenesis in a lung adenocarcinoma mouse model. DSTYK was downregulated in lung cancer tissues, and its expression was positively correlated with the survival of patients with lung adenocarcinoma. Taken together, these results demonstrate that the loss of DSTYK activates Wnt/β-catenin/LDHA signaling to promote the tumorigenesis of lung cancer and that DSTYK may be a therapeutic target.

Aberrant activation of ERK signaling is a hallmark of lung cancer. Although constitutively activating mutations of EGFR and KRAS contribute to the hyperactivation of ERK1/2, other mechanisms remain elusive. In this study, the zinc finger protein ZNF251 was found to be upregulated in clinical lung cancer samples, and it promoted the growth of lung cancer cells and the growth of primary lung KPC cells from mouse models (Ad‐Cre, KrasG12D, and P53f/f). In studying the molecular mechanism, ZNF251 was found to inhibit the expression of dual‐specificity phosphatase 6, a negative regulator of ERK activation, by directly binding to its promoter region. Taken together, our data indicate the tumor‐promoting effects of ZNF251 in lung cancer and suggest that ZNF251 is a therapeutic target. ZNF251 promotes lung cancer by activating ERK signaling.

Intense rainfall-induced shallow landslides can have severe consequences, including soil erosion and vegetation loss, making in-depth research essential for disaster risk management. However, vegetation recovery processes after shallow landslides and their influencing multivariate factors are not well known. This study aims to address this gap by investigating the vegetation recovery processes after shallow landslides and the impact of topography on this recovery. We focus on two regions in Japan: the Shobara district in Hiroshima Prefecture and the Obara district in Aichi Prefecture. The Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI) derived from long-term Landsat images, as well as aerial photographs and environmental datasets, are used to measure vegetation recovery. Then, statistical analysis and the Seasonal Autoregressive Integrated Moving Averages (SARIMA) model were employed to investigate the dynamic response of vegetation under different combinations of environmental conditions using NDVI and EVI time series. Historical aerial photographs and vegetation index trend analysis suggest that vegetation in the study areas will take more than ten years to return to a stable state. The results also demonstrate the influence of atmospheric and land cover conditions when monitoring vegetation response using NDVI and EVI. In Obara, concave and convergent terrain positively influenced NDVI, while non-steep, low-elevation, and north-facing terrain positively influenced EVI. In Shobara, gentle and northwest-facing slopes were positively correlated with NDVI, and gentle and west-facing slopes were positively correlated with EVI. SARIMA modeling found that NDVI is more suitable for modeling the middle and late stages of vegetation recovery within 10–25 years after the landslide. In comparison, EVI is better for modeling the early stage of vegetation recovery within 10 years after the landslide.

Quantifying vegetation responses after natural disasters helps clarify complex relationships between vegetation and surface processes such as soil erosion. The heterogenous post-disaster landscape offers a naturally stratified environment for this study. Existing research tends to be frequently monitored but small-scale or sporadically monitored but large-scale. The availability of high-quality and free satellite imagery bridges this gap by offering continuous, longer-term observations at the landscape scale. Here we take advantage of a dense Landsat time series to investigate landscape-scale vegetation response rates and factors at Unzen volcano, Japan. We do this by first investigating differences between two popular vegetation indices—The Normalized Difference Vegetation Index (NDVI) and the Normalized Burn Ratio (NBR), when applied to recovery studies. We then apply pixel-wise regressions to quantify spatio-temporal vegetation response and regression tree analyses to investigate drivers of recovery. Our findings showed that simple linear-log functions best model recovery rates reflecting primary succession trajectories caused by extreme disturbance and damage. Regression tree analyses showed that despite secondary disturbances, vegetation recovery in both the short and long-term is still dominated by eruption disturbance type and elevation. Finally, compared to NDVI, NBR is a better indicator of structural vegetation regrowth for the early years of revegetation.

Purpose To examine the level of stigma and identify its influencing factors among postoperative oral cancer patients in China. Methods In total, 274 postoperative oral cancer patients were recruited from a Grade A Tertiary Hospital in China using convenience sampling methods. Patients completed the Social Impact Scale (SIS), Medical Coping Mode Questionnaire (MCMQ), Social Support Rating Scale (SSRS), and General Self-efficacy Scale (GSE). Results Stigma reported by postoperative oral cancer patients was moderate (50.17 ± 21.24). Stepped multiple linear regression showed that the related factors influencing their feelings of stigma were educational level ( β  =  − 0.110, P  = 0.001), smoking ( β  =  − 0.152, P  < 0.001), betel quid ( β  =  − 0.120, P  = 0.001), tumor location ( β  =  − 0.390, P  < 0.001), tumor stage ( β  = 0.219, P  < 0.001), self-efficacy ( β  =  − 0.253, P  < 0.001), and confrontation ( β  =  − 0.117, P  = 0.001) and avoidance ( β  = 0.123, P  < 0.001), which explained 74.2% of the total variation in stigma ( F  = 99.378, P  < 0.001). Conclusions Stigma was positively predicted by tumor stage and avoidance but negatively predicted by education level, smoking, betel quid, tumor location, confrontation, and self-efficacy. Further work should focus on developing interventions to reduce stigma by improving protective factors and decreasing risk factors.

Esophageal squamous cell carcinoma (ESCC) is one of the most common lethal tumors in the world, and the development of new therapeutic targets is needed. Recent studies have shown that aerobic glycolysis, also known as the Warburg effect, mediated the anti-apoptotic effects in cancer cells. Lactate dehydrogenase A (LDHA) which executed the final step of aerobic lactate production has been reported to be involved in the tumor progression. However, the function of LDHA in ESCC has not been investigated. In this study, it was found that LDHA was up-regulated in ESCC clinical samples. Knockdown of the expression of LDHA inhibited cell growth and cell migration in vitro as well as tumorigenesis in vivo. With regard to the molecular mechanism, silencing the expression of LDHA was related to decreased AKT activation and cyclin D1 expression and increased cleavage of PARP and caspase 8. Taken together, our findings suggest that LDHA plays an important role in the progression of ESCC by modulating cell growth, and LDHA might be a potential therapeutic target in ESCC.

The use of chemotherapy has been proposed to increase the effectiveness of best supportive care (BSC) in patients with non-small cell lung cancer (NSCLC). Previous trials reported inconsistent findings regarding the efficacy and safety of chemotherapy on overall survival (OS) and treatment-related mortality. We performed a systematic review and meta-analysis to evaluate the effects of chemotherapy plus BSC versus BSC alone on survival of patients with NSCLC. We systematically searched PubMed, EmBase, and the Cochrane Central Register of Controlled Trials for relevant literature. All eligible studies included patients with NSCLC who had received chemotherapy and BSC or BSC alone. All eligible studies measured at least 1 of the following outcomes: OS or treatment-related mortality. Overall, patients that received chemotherapy plus BSC had significant longer OS than those that received BSC alone (HR, 0.76; 95%CI, 0.69-0.84; P<0.001). Additionally, chemotherapy plus BSC as compared to BSC alone resulted in a 28% RR reduction (95%CI: 12-40; P = 0.001) in 6-month mortality, 11% RR reduction (95%CI: 8-15; P<0.001) in 12-month mortality, and 5% RR reduction (95%CI: 1-8; P = 0.02) in 2-year mortality. Toxicity was greater in patients that received chemotherapy plus BSC. Chemotherapy plus BSC increased the OS and reduced the 6-month, 12-month, and 2-year mortality of NSCLC patients.

The alteration of metabolic processes has been found to have significant impacts on the development of hepatocellular carcinoma (HCC). Nevertheless, the effects of dysfunction of tyrosine metabolism on the development of HCC remains to be discovered. This research demonstrated that tyrosine hydroxylase (TH), which responsible for the initial and limiting step in the bio-generation of the neuro-transmitters dopamine and adrenaline, et al. was shown to be reduced in HCC. Increased expression of TH was found facilitates the survival of HCC patients. In addition, decreased TH indicated larger tumor size, much more numbers of tumor, higher level of AFP, and the presence of cirrhosis. TH effectively impairs the growth and metastasis of HCC cells, a process dependent on the phosphorylation of serine residues (S19/S40). TH directly binds to Smad2 and hinders the cascade activation of TGFβ/Smad signaling with the treatment of TGFβ1. In summary, our study uncovered the non-metabolic functions of TH in the development of HCC and proposes that TH might be a promising biomarker for diagnosis as well as an innovative target for metastatic HCC.

Hydroxymethylglutaryl coenzyme A reductase (HMGCR), the rate-limiting enzyme of mevalonate pathway, has been involved in the tumorigenesis of several tumor types. Our previous study has showed that statin, the inhibitor of HMGCR, inhibited the tumorigenecity of esophageal squamous cell carcinoma (ESCC) in vitro and in vivo. However, the function of HMGCR in the carcinogenesis of ESCC cells remains unknown. In this study, we have observed the up-regulation of HMGCR in ESCC tissues compared with the paired normal tissues. Over-expression of HMGCR in ESCC cells promoted cell growth and migration, while knockdown of the expression of HMGCR inhibited the growth, migration and colony formation of ESCC cells in vitro and in vivo. Furthermore, we found that oncogene Myc positively regulated the expression of HMGCR. Taken together, our study revealed the pivotal function of HMGCR and mevalonate pathway in the progression of ESCC and supported the clinical application of statin.

Inflammation and metabolic reprogramming are hallmarks of cancer. How inflammation regulates cancer metabolism remains poorly understood. In this study, we found that 3-hydroxy-3-methylglutaryl-CoA lyase (HMGCL), the enzyme that catalyzes the catabolism of leucine and promotes the synthesis of ketone bodies, was downregulated in lung cancer. Downregulation of HMGCL was associated with a larger tumor size and a shorter overall survival time. In a functional study, overexpression of HMGCL increased the content of β-hydroxybutyrate (β-HB) and inhibited the tumorigenicity of lung cancer cells, and deletion of HMGCL promoted de novo tumorigenesis in KP (Kras ;P53 ) mice. Mechanistically, tumor necrosis factor α (TNFα) treatment decreased the HMGCL protein level, and IKKβ interacted with HMGCL and phosphorylated it at Ser258, which destabilized HMGCL. Moreover, NEDD4 was identified as the E3 ligase for HMGCL and promoted its degradation. In addition, mutation of Ser258 to alanine inhibited the ubiquitination of HMGCL by NEDD4 and thus inhibited the anchorage-independent growth of lung cancer cells more efficiently than did wild-type HMGCL. In summary, this study demonstrated a link between TNFα-mediated inflammation and cancer metabolism.