Histone demethylase JMJD1A in cancer progression and therapeutic resistance

2022 ◽  
Author(s):  
Hee‐Young Jeon ◽  
Hyunju Ryu ◽  
Majid Pornour ◽  
Jianfei Qi
Keyword(s):  
Cancer Progression ◽  
Histone Demethylase ◽  
Therapeutic Resistance

scholarly journals Fibroblast activation protein targeted near infrared photoimmunotherapy (NIR PIT) overcomes therapeutic resistance in human esophageal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryoichi Katsube ◽  
Kazuhiro Noma ◽  
Toshiaki Ohara ◽  
Noriyuki Nishiwaki ◽  
Teruki Kobayashi ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Near Infrared ◽  
Fibroblast Activation Protein ◽  
Therapeutic Resistance ◽  
Fibroblast Activation ◽  
Human Esophageal Cancer

AbstractCancer-associated fibroblasts (CAFs) have an important role in the tumor microenvironment. CAFs have the multifunctionality which strongly support cancer progression and the acquisition of therapeutic resistance by cancer cells. Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer treatment that uses a highly selective monoclonal antibody (mAb)-photosensitizer conjugate. We developed fibroblast activation protein (FAP)-targeted NIR-PIT, in which IR700 was conjugated to a FAP-specific antibody to target CAFs (CAFs-targeted NIR-PIT: CAFs-PIT). Thus, we hypothesized that the control of CAFs could overcome the resistance to conventional chemotherapy in esophageal cancer (EC). In this study, we evaluated whether EC cell acquisition of stronger malignant characteristics and refractoriness to chemoradiotherapy are mediated by CAFs. Next, we assessed whether the resistance could be rescued by eliminating CAF stimulation by CAFs-PIT in vitro and in vivo. Cancer cells acquired chemoradiotherapy resistance via CAF stimulation in vitro and 5-fluorouracil (FU) resistance in CAF-coinoculated tumor models in vivo. CAF stimulation promoted the migration/invasion of cancer cells and a stem-like phenotype in vitro, which were rescued by elimination of CAF stimulation. CAFs-PIT had a highly selective effect on CAFs in vitro. Finally, CAF elimination by CAFs-PIT in vivo demonstrated that the combination of 5-FU and NIR-PIT succeeded in producing 70.9% tumor reduction, while 5-FU alone achieved only 13.3% reduction, suggesting the recovery of 5-FU sensitivity in CAF-rich tumors. In conclusion, CAFs-PIT could overcome therapeutic resistance via CAF elimination. The combined use of novel targeted CAFs-PIT with conventional anticancer treatments can be expected to provide a more effective and sensible treatment strategy.

Role of interleukin-6 in cancer progression and therapeutic resistance

Tumor Biology ◽  
2016 ◽  
Vol 37 (9) ◽  
pp. 11553-11572 ◽  
Author(s):  
Neeraj Kumari ◽  
B. S. Dwarakanath ◽  
Asmita Das ◽  
Anant Narayan Bhatt
Keyword(s):  
Cancer Progression ◽  
Interleukin 6 ◽  
Therapeutic Resistance

scholarly journals Spatiotemporal pH Heterogeneity as a Promoter of Cancer Progression and Therapeutic Resistance

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1026 ◽  
Author(s):  
David E. Korenchan ◽  
Robert R. Flavell
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Co2 Exchange ◽  
Therapeutic Resistance ◽  
Slow Time ◽  
Phenotypic Changes ◽  
Ph Buffering ◽  
Available Technology ◽  
Kinetics Of

Dysregulation of pH in solid tumors is a hallmark of cancer. In recent years, the role of altered pH heterogeneity in space, between benign and aggressive tissues, between individual cancer cells, and between subcellular compartments, has been steadily elucidated. Changes in temporal pH-related processes on both fast and slow time scales, including altered kinetics of bicarbonate-CO2 exchange and its effects on pH buffering and gradual, progressive changes driven by changes in metabolism, are further implicated in phenotypic changes observed in cancers. These discoveries have been driven by advances in imaging technologies. This review provides an overview of intra- and extracellular pH alterations in time and space reflected in cancer cells, as well as the available technology to study pH spatiotemporal heterogeneity.

scholarly journals KDM5 Histone Demethylase Activity Links Cellular Transcriptomic Heterogeneity to Therapeutic Resistance

Cancer Cell ◽  
2019 ◽  
Vol 35 (2) ◽  
pp. 330-332 ◽  
Author(s):  
Kunihiko Hinohara ◽  
Hua-Jun Wu ◽  
Sébastien Vigneau ◽  
Thomas O. McDonald ◽  
Kyomi J. Igarashi ◽  
...  
Keyword(s):  
Histone Demethylase ◽  
Therapeutic Resistance ◽  
Demethylase Activity

Abstract I16: KRAS and environmental signals regulate MYC to drive lineage plasticity, pancreas cancer progression, and therapeutic resistance

2019 ◽  
Author(s):  
Ellen Langer ◽  
Yulong Su ◽  
Meghan Joly ◽  
Brittany Allen-Petersen ◽  
Amy Farrell ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Pancreas Cancer ◽  
Therapeutic Resistance ◽  
Environmental Signals

scholarly journals Cancer-Associated Fibroblasts: Understanding Their Heterogeneity

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3108
Author(s):  
Kévin Louault ◽  
Rong-Rong Li ◽  
Yves A. DeClerck
Keyword(s):  
Cancer Progression ◽  
Immune Cell ◽  
Critical Role ◽  
Cell Reprogramming ◽  
Therapeutic Resistance ◽  
Cancer Associated Fibroblasts ◽  
Specific Function ◽  
Multiple Components ◽  
Extracellular Matrix Molecules ◽  
Heterogeneous Nature

The tumor microenvironment (TME) plays a critical role in tumor progression. Among its multiple components are cancer-associated fibroblasts (CAFs) that are the main suppliers of extracellular matrix molecules and important contributors to inflammation. As a source of growth factors, cytokines, chemokines and other regulatory molecules, they participate in cancer progression, metastasis, angiogenesis, immune cell reprogramming and therapeutic resistance. Nevertheless, their role is not fully understood, and is sometimes controversial due to their heterogeneity. CAFs are heterogeneous in their origin, phenotype, function and presence within tumors. As a result, strategies to target CAFs in cancer therapy have been hampered by the difficulties in better defining the various populations of CAFs and by the lack of clear recognition of their specific function in cancer progression. This review discusses how a greater understanding of the heterogeneous nature of CAFs could lead to better approaches aimed at their use or at their targeting in the treatment of cancer.

scholarly journals KDM4C Activity Modulates Cell Proliferation and Chromosome Segregation in Triple-Negative Breast Cancer

2016 ◽  
Vol 10 ◽  
pp. BCBCR.S40182 ◽  
Author(s):  
Jeison Garcia ◽  
Fernando Lizcano
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Chromosome Segregation ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Human Cancer ◽  
Histone Demethylase ◽  
Breast Cancer Cell Lines ◽  
Demethylase Activity

The Jumonji-containing domain protein, KDM4C, is a histone demethylase associated with the development of several forms of human cancer. However, its specific function in the viability of tumoral lineages is yet to be determined. This work investigates the importance of KDM4C activity in cell proliferation and chromosome segregation of three triple-negative breast cancer cell lines using a specific demethylase inhibitor. Immunofluorescence assays show that KDM4C is recruited to mitotic chromosomes and that the modulation of its activity increases the number of mitotic segregation errors. However, 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) cell proliferation assays demonstrate that the demethylase activity is required for cell viability. These results suggest that the histone demethylase activity of KDM4C is essential for breast cancer progression given its role in the maintenance of chromosomal stability and cell growth, thus highlighting it as a potential therapeutic target.

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