KDM2B is involved in the epigenetic regulation of TGF-β-induced epithelial–mesenchymal transition in lung and pancreatic cancer cell lines

Wanna-udom, Sasithorn; Terashima, Minoru; Suphakhong, Kusuma; Ishimura, Akihiko; Takino, Takahisa; Suzuki, Takeshi

doi:10.1074/jbc.ra120.015502

Cited by 14 publications

(8 citation statements)

References 44 publications

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“…As such, these cell lines have been used to study different aspects of pancreatic cancer, including DNA methylation, RNA splicing, histone modification, EMT, TGFβ signaling, and anticancer drug testing. [154][155][156][157] Results from these studies have shown correlations between gene expression, activation of specific cellular pathways, and drug response. In particular, the expression of MUC1 was found to induce drug resistance through the upregulation of multidrug resistance genes.…”

Section: Established (Commercial Cell Lines)mentioning

confidence: 99%

“…Their availability increase research efforts in the field of cancer research. As such, these cell lines have been used to study different aspects of pancreatic cancer, including DNA methylation, RNA splicing, histone modification, EMT, TGFβ signaling, and anticancer drug testing 154–157 . Results from these studies have shown correlations between gene expression, activation of specific cellular pathways, and drug response.…”

Section: Late Diagnosismentioning

confidence: 99%

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Advancements in Preclinical Models of Pancreatic Cancer

Salu,

Reindl

2024

Pancreas

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Pancreatic cancer remains one of the deadliest of all cancer types with a 5-year overall survival rate of just 12%. Preclinical models available for understanding the disease pathophysiology have evolved significantly in recent years. Traditionally, commercially available 2-dimensional cell lines were developed to investigate mechanisms underlying tumorigenesis, metastasis, and drug resistance. However, these cells grow as monolayer cultures that lack heterogeneity and do not effectively represent tumor biology. Developing patient-derived xenografts and genetically engineered mouse models led to increased cellular heterogeneity, molecular diversity, and tissues that histologically represent the original patient tumors. However, these models are relatively expensive and very timing consuming. More recently, the advancement of fast and inexpensive in vitro models that better mimic disease conditions in vivo are on the rise. Three-dimensional cultures like organoids and spheroids have gained popularity and are considered to recapitulate complex disease characteristics. In addition, computational genomics, transcriptomics, and metabolomic models are being developed to simulate pancreatic cancer progression and predict better treatment strategies. Herein, we review the challenges associated with pancreatic cancer research and available analytical models. We suggest that an integrated approach toward using these models may allow for developing new strategies for pancreatic cancer precision medicine.

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Section: Established (Commercial Cell Lines)mentioning

confidence: 99%

Section: Late Diagnosismentioning

confidence: 99%

Advancements in Preclinical Models of Pancreatic Cancer

Salu,

Reindl

2024

Pancreas

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“…4); очень редко, по одному случаю в каждой группе, обнаруживалась экспрессия десмина в единичных группах клеток. Миофибробласты являются главным стромальным компонентом и прогностическим маркером многих опухолей [8,9]. Они секретируют цитокины, протеазы и матриксные белки, обнаруживаются чаще в инвазивном крае опухоли [8,10].…”

Section: результаты и обсуждениеunclassified

“…Миофибробласты являются главным стромальным компонентом и прогностическим маркером многих опухолей [8,9]. Они секретируют цитокины, протеазы и матриксные белки, обнаруживаются чаще в инвазивном крае опухоли [8,10]. Ответственными за трансдифференцировку фибробластов в миофи-бробласты является трансформирующий фактор роста β (ТGF β), один из экстрацеллюлярных сигналов, индуцирующих ЭМТ [11,12].…”

Section: результаты и обсуждениеunclassified

Microenvironment influence on the development of epithelial-mesenchymal transformation in lung cancer

Kondratyk

Grekov

Seleznev³

2022

Vestn. Ross. univ. družby nar., Ser. Med.

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Relevance. Epithelial-mesenchymal transformation (EMT) largely determines the biological behavior and prognosis of cancers of various localizations. It is known that the determining role in the control and implementation of the transition of the epithelial phenotype to the mesenchymal belongs to the microenvironment. At the same time, the histochemical and microscopic characteristics of stromal elements remain unclear; therefore, the aim of our study was to establish the morphological features of the stroma that affect the development of EMT in lung cancer. Materials and Methods. We studied 32 cases of lung cancer with hematoxylin and eosin staining of sections, Alcian blue at pH 1.0 and 2.5, PAS reaction, as well as immunohistochemical studies with monoclonal antibodies to HMW, AE 1 / AE 3, cytokeratin 18, c-erb B 2, vimentin E-cadherin, alpha-smooth muscle actin, GFAP and chromogranin A, Ki-67. In 16 cases, there was widespread epithelial-mesenchymal transformation (EMT), in 14 cases - focal and in 2 cases EMT was absent. In half of the cases of widespread EMT, it was complete; among the cases of focal EMT, it was not complete. The transition from the epithelial to the mesenchymal phenotype was facilitated by the activation of the stroma, namely, the presence of myofibroblasts and alcianophilia of the extracellular matrix, inflammatory cell infiltration, expression of the epidermal growth factor receptor (c-erb B 2) in stromal cells, proliferation and neurogenic differentiation of stromal cells of stromal cells. Results and Discussion. The activated stroma correlates with the frequency of EMT. Thus, large areas of activated stroma with the presence of myofibroblasts and alcianophilia of the extracellular matrix are more common in cases of widespread EMT (14 out of 16-87.5 %) than in cases of focal EMT (4 out of 14-28.6 %). The differences are statistically significant, p 0.01. Inflammatory cell infiltration, which is the source of a signal for transformation, expression of the epidermal growth factor receptor (c-erb B 2) in stromal cells, proliferation, and neurogenic differentiation of stromal cells also correlated with the frequency of EMT. In all cases, the differences are statistically significant, p0.01. Conclusions. The data obtained indicate the undoubted influence of signals from the activated stroma on the development of epithelial-mesenchymal transformation of tumor cells.

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“…In addition, epigenetic regulations are considered as one of the critical mechanisms for EMT owing to its phenotypic plasticity ( 5 , 6 ). Thus, we have investigated and found the essential roles of histone methylation, histone ubiquitination, and long noncoding RNAs in the transcriptional regulatory network during EMT ( 7 , 8 , 9 , 10 ).…”

mentioning

confidence: 99%