Significance of Tsukushi in lung cancer

Yamada, Tatsuya; Ohta, Kunimasa; Motooka, Yamato; Fujita, Kosuke; Kudoh, Shinji; Tenjin, Yuki; Sato, Younosuke; Matsuo, Akira; Ikeda, Koei; Suzuki, Makoto; Ito, Takaaki

doi:10.1016/j.lungcan.2019.03.024

Cited by 12 publications

(9 citation statements)

References 46 publications

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“…Proteoglycans are an important component of the ECM and are associated with various cancers, such as liver, colon, and lung cancer. [ 55 – 57 ]. This is because when proteoglycans change dramatically, the tumor microenvironment facilitates cancer signaling and promotes tumor cell proliferation, angiogenesis, and migration [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis

Wei

Zeng

et al. 2020

Cancer Cell Int

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Background: The situation faced by breast cancer patients, especially those with triple-negative breast cancer, is still grave. More effective therapeutic targets are needed to optimize the clinical management of breast cancer. Although collagen type VIII alpha 1 chain (COL8A1) has been shown to be downregulated in BRIP1-knockdown breast cancer cells, its clinical role in breast cancer remains unknown. Methods: Gene microarrays and mRNA sequencing data were downloaded and integrated into larger matrices based on various platforms. Therefore, this is a multi-centered study, which contains 5048 breast cancer patients and 1161 controls. COL8A1 mRNA expression in breast cancer was compared between molecular subtypes. In-house immunohistochemistry staining was used to evaluate the protein expression of COL8A1 in breast cancer. A diagnostic test was performed to assess its clinical value. Furthermore, based on differentially expressed genes (DEGs) and coexpressed genes (CEGs) positively related to COL8A1, functional enrichment analyses were performed to explore the biological function and potential molecular mechanisms of COL8A1 underlying breast cancer. Results: COL8A1 expression was higher in breast cancer patients than in control samples (standardized mean difference = 0.79; 95% confidence interval [CI] 0.55-1.03). Elevated expression was detected in various molecular subtypes of breast cancer. An area under a summary receiver operating characteristic curve of 0.80 (95% CI 0.76-0.83) with sensitivity of 0.77 (95% CI 0.69-0.83) and specificity of 0.70 (95% CI 0.61-0.78) showed moderate capacity of COL8A1 in distinguishing breast cancer patients from control samples. Worse overall survival was found in the higher than in the lower COL8A1 expression groups. Intersected DEGs and CEGs positively related to COL8A1 were significantly clustered in the proteoglycans in cancer and ECM-receptor interaction pathways. Conclusions: Elevated COL8A1 may promote the migration of breast cancer by mediating the ECM-receptor interaction and synergistically interplaying with DEGs and its positively related CEGs independently of molecular subtypes. Several genes clustered in the proteoglycans in cancer pathway are potential targets for developing effective agents for triple-negative breast cancer.

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Section: Discussionmentioning

confidence: 99%

Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis

Wei

Zeng

et al. 2020

Cancer Cell Int

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“…RNA sequencing was conducted as established in a previous study conducted at Kumamoto University (Kumamoto, Japan; ref. 17). RNA sequencing was performed by the Liaison Laboratory Research Promotion Center (Kumamoto University, Kumamoto, Japan) as follows.…”

Section: Rna Sequencingmentioning

confidence: 99%

Extracellular Vesicles from Cancer-Associated Fibroblasts Containing Annexin A6 Induces FAK-YAP Activation by Stabilizing β1 Integrin, Enhancing Drug Resistance

et al. 2020

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◥Extracellular vesicles (EV) from cancer-associated fibroblasts (CAF) are composed of diverse payloads. Although CAFs impact the aggressive characteristics of gastric cancer cells, the contribution of CAF-EV to gastric cancer progression has not been elucidated. Here, we investigated the molecular mechanism of the changes in gastric cancer characteristics induced by CAF-EV. CAF abundance in gastric cancer tissues was associated with poor prognosis of patients with gastric cancer receiving chemotherapy. Moreover, CAF-EV induced tubular network formation and drug resistance of gastric cancer cells in the extracellular matrix (ECM). Comprehensive proteomic analysis of CAF-EV identified that Annexin A6 plays a pivotal role in network formation and drug resistance of gastric cancer cells in the ECM via activation of b1 integrin-focal adhesion kinase (FAK)-YAP. A peritoneal metastasis mouse model revealed that CAF-EV induced drug resistance in peritoneal tumors, and inhibition of FAK or YAP efficiently attenuated gastric cancer drug resistance in vitro and in vivo. These findings demonstrate that drug resistance is conferred by Annexin A6 in CAF-EV and provide a potential avenue for overcoming gastric cancer drug resistance through the inhibition of FAK-YAP signaling in combination with conventional chemotherapeutics.Significance: This study elucidates a novel molecular mechanism through which Annexin A6 in CAF-EV activates FAK-YAP by stabilizing b1 integrin at the cell surface of gastric cancer cells and subsequently induces drug resistance.

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“…Smoking has been positively correlated with lung tumor size during diagnosis suggesting an association between smoking and lung cancer [ 1 , 3 , [5] , [6] , [7] , [8] ]. EGFR (Epidermal Growth Factor Receptor) mutation status is now examined even if the patient is a former smoker because of the proven benefit these therapies have and the substantial improvement seen in patients over standard chemotherapy [ 5 , 6 , [9] , [10] , [11] ]. Those patients who present with localized disease represent the subset that undergo surgical resection and for which extensive molecular analyses have been performed.…”

Section: Introductionmentioning

confidence: 99%

Collagen modifying enzyme P4HA1 is overexpressed and plays a role in lung adenocarcinoma

Robinson

Chakravarthi

Agarwal

et al. 2021

Translational Oncology

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Significance of Tsukushi in lung cancer

Cited by 12 publications

References 46 publications

Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis

Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis

Extracellular Vesicles from Cancer-Associated Fibroblasts Containing Annexin A6 Induces FAK-YAP Activation by Stabilizing β1 Integrin, Enhancing Drug Resistance

Collagen modifying enzyme P4HA1 is overexpressed and plays a role in lung adenocarcinoma

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