Glutathione peroxidase 8 expression on cancer cells and cancer‐associated fibroblasts facilitates lung cancer metastasis
Yulian XuLuo‐Wei YuanXiaoming JiangMin‐Xia SuMu‐Yang HuangYu‐Chi ChenLele ZhangXiuping ChenHong‐Jian ZhuJin‐Jian Lu
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Abstract Lung cancer is the leading cause of cancer death worldwide, of which lung adenocarcinoma (LUAD) is the most common subtype. Metastasis is the major cause of poor prognosis and mortality for lung cancer patients, which urgently needs great efforts to be further explored. Herein, glutathione peroxidase 8 (GPX8) was identified as a novel potential pro‐metastatic gene in LUAD metastatic mice models from GEO database. GPX8 was highly expressed in tumor tissues, predicting poor prognosis in LUAD patients. Knockdown of GPX8 inhibited LUAD metastasis in vitro and in vivo, while it did not obviously affect tumor growth. Knockdown of GPX8 decreased the levels of p‐FAK and p‐Paxillin and disturbed the distribution of focal adhesion. Furthermore, GPX8 was overexpressed in cancer‐associated fibroblast (CAF) and associated with CAF infiltration in tumor microenvironment of lung cancer. GPX8 silence on fibroblasts suppressed lung cancer cell migration in the coculture system. BRD2 and RRD4 were the potential transcriptionally regulators for GPX8. Bromodomain extra‐terminal inhibitor JQ1 downregulated GPX8 expression and suppressed lung cancer cell migration. Our findings indicate that highly expressed GPX8 in lung cancer cells and fibroblasts functions as a pro‐metastatic factor in lung cancer. JQ1 is identified as a potential inhibitor against GPX8‐mediated lung cancer metastasis.Lung cancer is still a leading cause of cancer mortality in the world. The incidence of lung cancer in developed countries started to decrease mainly due to global anti-smoking campaigns. However, the incidence of lung cancer in women has been increasing in recent decades for various reasons. Furthermore, since the screening of lung cancer is not as yet very effective, clinically applicable molecular markers for early diagnosis are much required. Lung cancer in women appears to have differences compared with that in men, in terms of histologic types and susceptibility to environmental risk factors. This suggests that female lung cancer can be derived by carcinogenic mechanisms different from those involved in male lung cancer. Among female lung cancer patients, many are non-smokers, which could be studied to identify alternative carcinogenic mechanisms independent from smoking-related ones. In this paper, we reviewed molecular susceptibility markers and genetic changes in lung cancer tissues observed in female lung cancer patients, which have been validated by various studies and will be helpful to understand the tumorigenesis of lung cancer.
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Cancer-Associated Fibroblasts
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Abstract Cancer metastasis is the leading cause of cancer‐related death. It is a complex, inefficient, and multistep process related to poor prognosis and high mortality of patients. Increasing evidence has shown that metabolic programming is a recognized hallmarker of cancer, plays a critical role in cancer metastasis. Metabolism alterations of glucose, lipid, and amino acid provide cancer cells with energy and substances for biosynthesis, maintain biofunctions and significantly affect proliferation, invasion, and metastasis of cancer cells. Tumor microenvironment (TME) is a complex system formed by varieties of cellular and noncellular elements. Nontumor cells in TME also undergo metabolic reprogramming or respond to metabolites to promote migration and invasion of cancer cells. A comprehensive understanding of the regulatory mechanism in metastasis from the metabolic reprogramming aspect is required to develop new therapeutic strategies combatting cancer metastasis. This review illustrates the metabolic reprogramming and interaction of cancer cells and nontumor cells in the TME, and the development of treatment strategies targeting metabolism alterations.
Reprogramming
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Lung cancer has been viewed as the most common malignant cancer with high incidence, mortality and poor survival all over the world. A lot of investigations indicated there are significant gender-associated differences in lung cancer in several characteristics such as epidemiology, pathology, clinical outcome and prognosis. The insight into these differences may help to clarify the gender-associated characteristics of lung cancer, and to drawn out new approach for treatment and prevent of lung cancer depending on gender-associated characteristics. Furthermore, study on mechanism of gender-associated characteristics may even help to illuminate the pathogenesis of lung cancer.
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Tobacco smoke
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The tumor immune microenvironment has been a research hot spot in recent years. The cytokines and metabolites in the microenvironment can promote the occurrence and development of tumor in various ways and help tumor cells get rid of the surveillance of the immune system and complete immune escape. Many studies have shown that the existence of tumor microenvironment is an important reason for the failure of immunotherapy. The impact of the tumor microenvironment on tumor is a systematic study. The current research on this aspect may be only the tip of the iceberg, and a relative lack of integrity, may be related to the heterogeneity of tumor. This review mainly discusses the current status of glucose metabolism and lipid metabolism in the tumor microenvironment, including the phenotype of glucose metabolism and lipid metabolism in the microenvironment; the effects of these metabolic methods and their metabolites on three important immune cells Impact: regulatory T cells (Tregs), tumor-associated macrophages (TAM), natural killer cells (NK cells); and the impact of metabolism in the targeted microenvironment on immunotherapy. At the end of this article,the potential relationship between Ferroptosis and the tumor microenvironment in recent years is also briefly described.
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Objective:To investigate the expression level of adrenomedulin(ADM)in lung cancer patients,the relationship be- tween ADM and the pathological type and stage of lung cancer.Methods:We determined the content of ADM in plasma of 20 healthy adults,24 non-lung cancer patients and 61 lung cancer patients by use of radioimmunoassay.Results:The content of ADM in the plasma of healthy control group was 30.25±8.12 pg/L,lung cancer group was 40.17±19.23 pg/L,there was significant difference between them(P＜0.05) ;The content of ADM in the plasma of non-lung cancer group was 27.94±6.75 pg/L,compared with lung cancer group,there was significant difference(P＜0.01 );Small cell lung cancer group compared with non-small cell lung cancer group,the content of ADM in plasma had no significant difference(P＞0.{)5) ;Ⅰ-Ⅲstage of lung cancer group compared withⅣstage group,the content of ADM in plasma had significant difference(P＜0.05).Conclusion: The expression level of ADM in plasma of lung cancer increased,the expression level of ADM was correlated with the stage of lung cancer and distant metastasis,No correlation was found between ADM level and the pathological type of lung cancer. Therefore,detecting ADM in plasma had great value in lung cancer diagnosis and staging,and provided a new way to lung cancer diagnosis.
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