Fibroblast-specific ERK5 deficiency changes tumor vasculature and exacerbates tumor progression in a mouse model

Imanishi, Masaki; Yamakawa, Yusuke; Fukushima, Keijo; Ikuto, Raiki; Maegawa, Akiko; Izawa‐Ishizawa, Yuki; Horinouchi, Yuya; Kondo, Masateru; Kishuku, Masatoshi; Goda, Mitsuhiro; Zamami, Yoshito; Takechi, Kenshi; Chuma, Masayuki; Ikeda, Yasumasa; Tsuchiya, Koichiro; Fujino, Hiromichi; Tsuneyama, Koichi; Ishizawa, Keisuke

doi:10.1007/s00210-020-01859-5

Cited by 3 publications

(3 citation statements)

References 26 publications

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“…Certain proofs have revealed that ERK5-mediated signal transduction facilitates the development of many tumors like gastric [40], bladder [12, 23], colon [41], and lung cancers [42]. ERK5 can be stimulated by receptor tyrosine kinases and other stimulating substances like benzidine [12, 17–22].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, certain researches revealed that ERK5 regulated benzidine-mediated urocystic EMT and that ERK5 inhibition reversed EMT alterations [12, 22]. In a mouse model, fibroblast-specific ERK5 deficiency enhanced tumor vessel formation and increased the number of activated fibroblast, and it exacerbated tumor progression [41]. Sánchez-Fdez et al indicated that the elevated contents of MEK5/ERK5 were related to unsatisfactory prognoses in pulmonary carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…Certain proofs have revealed that ERK5-mediated signal transduction facilitates the development of many tumors like gastric [40], bladder [12,23], colon [41], and lung cancers [42].…”

Section: Skopelitou Et Al Indicated That Pcna Expression Was Closely ...mentioning

confidence: 99%

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Benzidine Induces Proliferation of UMUC3 Bladder Cancer Cells Through Activation of ERK5 Pathway

Sun

Zhang

Tang

et al. 2022

Preprint

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Mounting evidences have revealed that benzidine, a known human carcinogen, is a pivotal risk factor for bladder cancer (BC). Dysregulated cell proliferation serves as a pivotal pathophysiological step in BC development. The potential mechanisms of MAPK pathways, particularly extracellular regulated protein kinases 5 (ERK5), regarding the modulation of benzidine-elicited cell proliferation are still elusive. Herein, human BC cells UMUC-3 were exposed to indicated levels of benzidine for 5 days. Cell growth, cell cycle progression, cell cycle-related, MAPK genetic expression, and related protein contents were investigated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test, flow cytometry, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and western blotting (WB), respectively. XMD8-92 (a specific suppressor of ERK5) and small interfering RNA (siRNA) were utilized to identify the roles of ERK5. Our results illustrated that benzidine elevated the proliferative ability of UMUC3 cells and accelerated the cell cycle transition from G1 to S phase, and it increased the expressions of cyclin D1 and proliferating cell nuclear antigen (PCNA) and reduced the expression of p21. Meanwhile, benzidine treatment resulted in the activation of ERK5 pathway and activator protein 1 (AP-1) proteins. In addition, benzidine-elicited cell proliferation and ERK5 stimulation were fully inhibited by XMD8-92 and siRNAs specific to ERK5. Taken together, these results demonstrated that ERK5-mediated cell proliferation was tightly related to benzidine-assoicated BC development, which established the foundation for targeting the ERK5 pathway in BC treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Benzidine Induces Proliferation of UMUC3 Bladder Cancer Cells Through Activation of ERK5 Pathway

Sun

Zhang

Tang

et al. 2022

Preprint

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CA9 and PRELID2; hypoxia-responsive potential therapeutic targets for pancreatic ductal adenocarcinoma as per bioinformatics analyses

Imanishi,

Inoue,

Fukushima

et al. 2023

Journal of Pharmacological Sciences

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Distinct Transcriptional Programs in Ascitic and Solid Cancer Cells Induce Different Responses to Chemotherapy in High-Grade Serous Ovarian Cancer

Loret

Vandamme

Coninck

et al. 2022

Molecular Cancer Research

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High-grade serous ovarian cancer (HGSOC) is responsible for the largest number of ovarian cancer deaths. The frequent therapy resistant relapses necessitate a better understanding of mechanisms driving therapy resistance. Therefore, we mapped more than hundred thousand cells of HGSOC patients in different phases of the disease, using single-cell RNA sequencing. Within patients, we compared chemonaive with chemotreated samples. As such, we were able to create a single-cell atlas of different HGSOC lesions and their treatment. This revealed a high intra-patient concordance between spatially distinct metastases. In addition, we found remarkable baseline differences in transcriptomics of ascitic and solid cancer cells, resulting in a different response to chemotherapy. Moreover, we discovered different robust subtypes of cancer-associated fibroblasts (CAFs) in all patients. Besides inflammatory CAFs (iCAFs), vascular CAFs (vCAFs) and matrix CAFs (mCAFs), we identified a new CAF subtype that was characterized by high expression of STAR, TSPAN8 and ALDH1A1 and clearly enriched after chemotherapy. Together, tumor heterogeneity in both cancer and stromal cells contributes to therapy resistance in HGSOC and could form the basis of novel therapeutic strategies that differentiate between ascitic and solid disease. Implications: The newly characterized differences between ascitic and solid cancer cells before and after chemotherapy could inform novel treatment strategies for metastatic HGSOC.

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Fibroblast-specific ERK5 deficiency changes tumor vasculature and exacerbates tumor progression in a mouse model

Cited by 3 publications

References 26 publications

Benzidine Induces Proliferation of UMUC3 Bladder Cancer Cells Through Activation of ERK5 Pathway

Benzidine Induces Proliferation of UMUC3 Bladder Cancer Cells Through Activation of ERK5 Pathway

CA9 and PRELID2; hypoxia-responsive potential therapeutic targets for pancreatic ductal adenocarcinoma as per bioinformatics analyses

Distinct Transcriptional Programs in Ascitic and Solid Cancer Cells Induce Different Responses to Chemotherapy in High-Grade Serous Ovarian Cancer

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