FH535 increases the radiosensitivity and reverses epithelial-to-mesenchymal transition of radioresistant esophageal cancer cell line KYSE-150R

Su, Huafang; Jin, Xiance; Zhang, Xuebang; Li, Zhao; Lin, Bing; Li, Lili; Fei, Zhenghua; Shen, Lanxiao; Fang, Yun; Pan, Huanle; Xie, Congying

doi:10.1186/s12967-015-0464-6

Cited by 51 publications

(43 citation statements)

References 28 publications

(26 reference statements)

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“…Preliminary evidence indicates that Wnt/β-catenin signaling may trigger epithelial to mesenchymal transition (EMT), which has been implicated in increased resistance to radiotherapy (28,35–38). In our gene expression data, we observed an overexpression of genes associated with EMT in resistant cell populations, underscoring the importance of the Wnt/β-catenin EMT axis (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Chemoradiotherapy Resistance in Colorectal Cancer Cells is Mediated by Wnt/β-catenin Signaling

Emons

Spitzner

Reineke

et al. 2017

Molecular Cancer Research

114

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Activation of Wnt/β-catenin signaling plays a central role in the development and progression of colorectal cancer (CRC). The Wnt-transcription factor, TCF7L2, is overexpressed in primary rectal cancers that are resistant to chemoradiotherapy (CRT) and TCF7L2 mediates resistance to CRT. However, it is unclear whether the resistance is mediated by a TCF7L2 inherent mechanism or Wnt/β-catenin signaling in general. Here, inhibition of β-catenin by siRNAs or a small molecule inhibitor (XAV-939) resulted in sensitization of CRC cells to CRT. To investigate the potential role of Wnt/β-catenin signaling in controlling therapeutic responsiveness, non-tumorigenic RPE-1 cells were stimulated with Wnt-3a, a physiological ligand of Frizzled-receptors, which increased resistance to CRT. This effect could be recapitulated by overexpression of a degradation-resistant mutant of β-catenin (S33Y), also boosting resistance of RPE-1 cells to CRT, which was, conversely, abrogated by siRNA-mediated silencing of β-catenin. Consistent with these findings, higher expression levels of active β-catenin were observed as well as increased TCF/LEF reporter activity in SW1463 cells that evolved radiation resistance due to repeated radiation treatment. Global gene expression profiling identified several altered pathways, including PPAR signaling and other metabolic pathways, associated with cellular response to radiation. In summary, aberrant activation of Wnt/β-catenin signaling not only regulates the development and progression of colorectal cancer, but also mediates resistance of rectal cancers to chemoradiotherapy. Implications Targeting Wnt/β-catenin signaling or one of the downstream pathways represents a promising strategy to increase response to CRT.

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Section: Discussionmentioning

confidence: 99%

Chemoradiotherapy Resistance in Colorectal Cancer Cells is Mediated by Wnt/β-catenin Signaling

Emons

Spitzner

Reineke

et al. 2017

Molecular Cancer Research

114

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“…Knockdown of NEAT1 could sensitize NPC cells to radiation in vitro . NEAT1 may also induce EMT phenotype, which is a key contributor to radioresistance [84]. In addition, there was a physical interaction between NEAT1 and miR-204 in NPC cells.…”

Section: Oncogenic Lncrnasmentioning

confidence: 99%

Functions and Roles of Long-Non-Coding RNAs in Human Nasopharyngeal Carcinoma

Hann²

2018

Cell Physiol Biochem

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Nasopharyngeal carcinoma (NPC) is one of the most common cancers originating in the nasopharynx and occurring at high frequency in South-eastern Asia and North Africa. Long non-coding RNAs (lncRNAs) are a class of non-protein-coding RNA molecules and key regulators of developmental, physiological, and pathological processes in humans. Emerging studies have shown that lncRNAs play critical roles in tumorgenicity and cancer prognosis. With the development of deep sequencing analyses, an extensive amount of functional lncRNAs have been discovered in nasopharyngeal carcinoma tissues and cell lines. However, the roles and mechanisms of aberrantly expressed lncRNAs in the pathogenesis of NPC are not fully understood. In this review, we briefly illustrate the concept, identification, functional characterization, and summarize recent advancements of biological functions of lncRNAs with heterogeneous mechanistic characterization and their involvement in NPC. Then, we describe individual lncRNAs that have been associated with tumorgenesis, growth, invasion, cancer stem cell differentiation, metastasis, drug resistance and discuss the strategies of their therapeutic manipulation in NPC. We also review the emerging insights into the role of lncRNAs and their potential as biomarkers and therapeutic targets for novel treatment paradigms. Finally, we highlight the up-to-date of clinical information involving lncRNAs and future directions in the linking lncRNAs to potential gene therapies, and how modifications of lncRNAs can be exploited for prevention and treatment of NPC.

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“…A number of studies have confirmed that radiation can induce EMT or phenotypic changes similar to EMT (73–75). For example, in KYSE-150R cells, a radioresistant esophageal cancer cell line, phenotypic changes similar to EMT are induced by radiation, including decreased E-cadherin and increased Snail and Twist expressions (76), which are also observed in nasopharyngeal carcinoma (77) and colorectal cancer (78). Furthermore, a number of pathways have been reported to contribute to radiation-induced EMT of cancer cells.…”

Section: Radiation Induces Emt In Cancermentioning

confidence: 99%

Radiation induces the generation of cancer stem cells: A novel mechanism for cancer radioresistance

Zhou

Gao

et al. 2016

Oncology Letters

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Radioresistance remains a major obstacle for the radiotherapy treatment of cancer. Previous studies have demonstrated that the radioresistance of cancer is due to the existence of intrinsic cancer stem cells (CSCs), which represent a small, but radioresistant cell subpopulation that exist in heterogeneous tumors. By contrast, non-stem cancer cells are considered to be radiosensitive and thus, easy to kill. However, recent studies have revealed that under conditions of radiation-induced stress, theoretically radiosensitive non-stem cancer cells may undergo dedifferentiation subsequently obtaining the phenotypes and functions of CSCs, including high resistance to radiotherapy, which indicates that radiation may directly result in the generation of novel CSCs from non-stem cancer cells. These findings suggest that in addition to intrinsic CSCs, non-stem cancer cells may also contribute to the relapse and metastasis of cancer following transformation into CSCs. This review aims to investigate the radiation-induced generation of CSCs, its association with epithelial-mesenchymal transition and its significance with regard to the radioresistance of cancer.

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FH535 increases the radiosensitivity and reverses epithelial-to-mesenchymal transition of radioresistant esophageal cancer cell line KYSE-150R

Cited by 51 publications

References 28 publications

Chemoradiotherapy Resistance in Colorectal Cancer Cells is Mediated by Wnt/β-catenin Signaling

Chemoradiotherapy Resistance in Colorectal Cancer Cells is Mediated by Wnt/β-catenin Signaling

Functions and Roles of Long-Non-Coding RNAs in Human Nasopharyngeal Carcinoma

Radiation induces the generation of cancer stem cells: A novel mechanism for cancer radioresistance

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