scholarly journals Fractionated irradiation-induced EMT-like phenotype conferred radioresistance in esophageal squamous cell carcinoma

2016 ◽  
Vol 57 (4) ◽  
pp. 370-380 ◽  
Author(s):  
Hongfang Zhang ◽  
Honglei Luo ◽  
Zhenzhen Jiang ◽  
Jing Yue ◽  
Qiang Hou ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Line ◽  
Squamous Cell ◽  
Growth Promotion ◽  
Matricellular Protein ◽  
Parental Cell Line ◽  
Fractionated Irradiation ◽  
Mesenchymal Transition

Abstract The efficacy of radiotherapy, one major treatment modality for esophageal squamous cell carcinoma (ESCC) is severely attenuated by radioresistance. Epithelial-to-mesenchymal transition (EMT) is a cellular process that determines therapy response and tumor progression. However, whether EMT is induced by ionizing radiation and involved in tumor radioresistance has been less studied in ESCC. Using multiple fractionated irradiation, the radioresistant esophageal squamous cancer cell line KYSE-150R had been established from its parental cell line KYSE-150. We found KYSE-150R displayed a significant EMT phenotype with an elongated spindle shape and down-regulated epithelial marker E-cadherin and up-regulated mesenchymal marker N-cadherin in comparison with KYSE-150. Furthermore, KYSE-150R also possessed some stemness-like properties characterized by density-dependent growth promotion and strong capability for sphere formation and tumorigenesis in NOD-SCID mice. Mechanical studies have revealed that WISP1, a secreted matricellular protein, is highly expressed in KYSE-150R and mediates EMT-associated radioresistance both in ESCC cells and in xenograft tumor models. Moreover, WISP1 has been demonstrated to be closely associated with the EMT phenotype observed in ESCC patients and to be an independent prognosis factor of ESCC patients treated with radiotherapy. Our study highlighted WISP1 as an attractive target to reverse EMT-associated radioresistance in ESCC and can be used as an independent prognostic factor of patients treated with radiotherapy.

scholarly journals Pharmacological Inhibition of PP2A Overcomes Nab-Paclitaxel Resistance by Downregulating MCL1 in Esophageal Squamous Cell Carcinoma (ESCC)

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4766
Author(s):  
Qi Song ◽  
Herui Wang ◽  
Dongxian Jiang ◽  
Chen Xu ◽  
Jing Cui ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Tumor Growth ◽  
Cell Carcinoma ◽  
Cell Line ◽  
Cell Lines ◽  
Squamous Cell ◽  
Resistant Cell ◽  
Parental Cell Line ◽  
Pharmacological Inhibition

Paclitaxel-based chemotherapy is a treatment option for advanced esophageal squamous cell carcinoma (ESCC). However, the development of chemoresistance leads to treatment failure, and the underlying mechanism remains elusive. We investigated the mechanisms of nanoparticle albumin-bound paclitaxel (nab-PTX) resistance by establishing three nab-PTX resistant ESCC cell lines. Proteomics analysis revealed higher oxidative phosphorylation (OXPHOS) in resistant cell line DR150 than in its parental cell line KYSE150, which is likely caused by stabilized anti-apoptotic protein MCL1. Additionally, we discovered the elevated activity of protein phosphatase 2A (PP2A), the phosphatase that dephosphorylates and stabilizes MCL1, in nab-PTX resistant cell lines. Pharmacological inhibition of PP2A with small molecule compound LB-100 decreased MCL1 protein level, caused more apoptosis in nab-PTX resistant ESCC cell lines than in the parental cells in vitro, and significantly inhibited the tumor growth of nab-PTX resistant xenografts in vivo. Moreover, LB-100 pretreatment partially restored nab-PTX sensitivity in the resistant cell lines and synergistically inhibited the tumor growth of nab-PTX resistant xenografts with nab-PTX. In summary, our study identifies a novel mechanism whereby elevated PP2A activity stabilizes MCL1 protein, increases OXPHOS, and confers nab-PTX resistance, suggesting that targeting PP2A is a potential strategy for reversing nab-PTX resistance in patients with advanced ESCC.

Establishment and Characterization of HKESC-1, a New Cancer Cell Line from Human Esophageal Squamous Cell Carcinoma

2000 ◽  
Vol 118 (2) ◽  
pp. 112-120 ◽  
Author(s):  
Ying-Chuan Hu ◽  
King Y Lam ◽  
Thomas S.K Wan ◽  
Wei-Gang Fang ◽  
Edmond S.K Ma ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Line ◽  
Cancer Cell ◽  
Squamous Cell ◽  
Cancer Cell Line

Genomics of esophageal squamous cell carcinoma in African Americans.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16552-e16552
Author(s):  
Robert George Wadleigh ◽  
Nirmala Akula ◽  
Susan Lazerow ◽  
Gustavo Marino ◽  
Suman Chauhan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
African Americans ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Mutation Rate ◽  
Squamous Cell ◽  
Copy Number ◽  
Copy Number Variations ◽  
Mesenchymal Transition ◽  
Copy Number Changes

e16552 Background: Esophageal cancer (EC) is one of the most lethal cancers with 90% mortality rate. Uneven Worldwide geographical distribution and varying etiologic factors contribute to the heterogenic nature of EC worldwide. In the US, 75% esophageal squamous cell carcinoma (ESCC) is diagnosed in African Americans (AA). However, despite comprehensive and multi-geographical efforts to understand the genomic basis of ESCC, the knowledge of molecular and genetic mechanisms leading to genomic subtyping of AA has been limited due to the underrepresentation of AAs in these studies. We hypothesized that the differences in mutational events in AA ESCC might, in part, cause the disparity in outcome and the mutational events may determine treatment options. Methods: Whole exome sequencing (WES) of matched- tumor and normal-cell DNA from late-stage ESCC of ten AA patients were performed by using Agilent SureSelect XT Human All Exon V6+UTR. Somatic variants per tumor samples called by two or more methods (Mutect2, VarScan2, and Strelka2) were combined and used for downstream population filtering. Somatic copy number changes were determined by using CNVKit in SevenBridges Genomics. Results: Somatic variants called by two or more algorithms filtered and sorted for rare mutations (equal to or less than 1% African originated population frequency) demonstrated an average of 23 nonsynonymous mutations per MB in high mutation rate AA ESCC. The remaining four samples had two or fewer nonsynonymous mutations per MB. TP53 was one of the most frequently mutated gene with 50% of mutation frequency. ARID2 mutated in 30%, EP300 in 20%, and RB1 in 10% of our cohort. Multiple amplified and deleted regions ranging from 94 to 46 were observed in seven samples in contrast to three samples that were silent in terms of copy number variations ranging from 29 to 9. Significant CNV were mostly seen in proliferation, cell cycle and checkpoint genes, squamous cell homeostasis, epithelial to mesenchymal transition, invasion and metastasis, receptor tyrosine kinase and signaling pathways, chromatin remodeling, detoxification, RNA/DNA editing and angiogenesis. Conclusions: WES of ten AA ESCC samples demonstrated a higher mutation rate in a group of patients with many passenger mutations and complex and recurrent copy number changes that affect oncogenic driver genes, which might suggest enhanced subtyping of ESCC in AA.

PLK1 Promotes Invasion of Esophageal Squamous Cell Carcinoma Cells through Inducing Epithelial-Mesenchymal Transition

2014 ◽  
Vol 998-999 ◽  
pp. 279-282 ◽  
Author(s):  
Ji Yu Ju ◽  
Wen Jing Yu ◽  
Chun Ling Zhao
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Epithelial Mesenchymal Transition ◽  
Mrna Level ◽  
Mesenchymal Transition ◽  
Stable Transfectants ◽  
Tumorigenesis And Progression

PLK1 has been implicated in tumorigenesis and progression. The role of PLK1 in carcinogenesis has not been fully understood. In our study, we established PLK1-overexpressed stable transfectants in esophageal squamous cell carcinoma (ESCC) cells. Ectopic overexpression of PLK1 enhanced invasiveness of ESCC cells. Compared with the empty vector-transfected cells, PLK overexpression dramatically decreased expression of E-cadherin and increased expression of Vimentin in ESCC cells. Furthermore, Vimentin was also significantly increased at mRNA level in PLK overexpressed ESCC cells. These data suggest that PLK1 promotes invasion of ESCC cells by inducing EMT.

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