CDKN2A inhibits formation of homotypic cell-in-cell structures

Liang, Jianqing; Fan, Jia; Wang, Manna; Niu, Zubiao; Zhang, Zhengrong; Yuan, Long; Tai, Yoshiaki; Chen, Zhaolie; Song, Santai; Wang, Xiaoning; Liu, Xiaoqing; Huang, Hongyan; Sun, Qiang

doi:10.1038/s41389-018-0056-4

Cited by 39 publications

(42 citation statements)

References 25 publications

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“…Indeed, CDKN2A status was found to be associated with various cancers [ 35 – 40 ]. A recent study identified CDKN2A as a tumor suppressor whose inactivation promoted homotypic cell-in-cell formation in human cancer cells [ 41 ]. Our analysis also suggested that CDKN2A might be a potential biomarker of recurrence in early-stage NSCLC.…”

Section: Discussionmentioning

confidence: 99%

Targeted next-generation sequencing reveals recurrence-associated genomic alterations in early-stage non-small cell lung cancer

et al. 2018

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PurposeThe identification of genomic alterations related to recurrence in early-stage non-small cell lung cancer (NSCLC) patients may help better stratify high-risk individuals and guide treatment strategies. This study aimed to identify the molecular biomarkers of recurrence in early-stage NSCLC.ResultsOf the 42 tumors evaluable for genomic alterations, TP53 and EGFR were the most frequent alterations with population frequency 52.4% and 50.0%, respectively. Fusion genes were detected in four patients, which had lower mutational burden and relatively better genomic stability. EGFR mutation and fusion gene were mutually exclusive in this study. CDKN2A, FAS, SUFU and SMARCA4 genomic alterations were only observed in the relapsed patients. Increased copy number alteration index was observed in early relapsed patients. Among these genomic alterations, early-stage NSCLCs harboring CDKN2A, FAS, SUFU and SMARCA4 genomic alterations were found to be significantly associated with recurrence. Some of these new findings were validated using The Cancer Genome Atlas (TCGA) dataset.ConclusionsThe genomic alterations of CDKN2A, FAS, SUFU and SMARCA4 in early-stage NSCLC are found to be associated with recurrence, but confirmation in a larger independent cohort is required to define the clinical impact.Materials and MethodsPaired primary tumor and normal lung tissue samples were collected for targeted next-generation sequencing analysis. A panel targets exons for 440 genes was used to assess the mutational and copy number status of selected genes in three clinically relevant groups of stage I/II NSCLC patients: 1) Early relapse; 2) Late relapse; and 3) No relapse.

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Section: Discussionmentioning

confidence: 99%

Targeted next-generation sequencing reveals recurrence-associated genomic alterations in early-stage non-small cell lung cancer

et al. 2018

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“…Another tumour suppressor involved in entosis is CDKN2A . Inactivation of CDKN2A promoted entosis and CDKN2A expression and was inversely correlated to CIC formation in breast cancers [52]. Oncogenes have also been implicated in entosis and overexpression of KRAS V12 or c-Myc was shown to promote the formation of the CIC structures [15,53].…”

Section: The Relationship Between Cic Structures and Tumour Promotersmentioning

confidence: 99%

Biological relevance of cell-in-cell in cancers

Mackay

Müller

2019

Biochemical Society Transactions

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Cell-in-cell (CIC) is a term used to describe the presence of one, usually living, cell inside another cell that is typically considered non-phagocytic. Examples of this include tumour cells inside tumour cells (homotypic), mesenchymal stem cells inside tumour cells (heterotypic) or immune cells inside tumour cells (heterotypic). CIC formation can occur in cell lines and in tissues and it has been most frequently observed during inflammation and in cancers. Over the past 10 years, many researchers have studied CIC structures and a few different models have been proposed through which they can be formed, including entosis, cannibalism and emperipolesis among others. Recently, our laboratory discovered a role for mutant p53 in facilitating the formation of CIC and promoting genomic instability. These data and research by many others have uncovered a variety of molecules involved in CIC formation and have started to give us an idea of why they are formed and how they could contribute to oncogenic processes. In this perspective, we summarise current literature and speculate on the role of CIC in cancer biology.

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“…Several chemokines, cytokines and angiogenic factors produced by neutrophils may result in inflammatory cell recruitment and activation that crucially impact the tumor microenvironment, which could facilitate tumor cell proliferation, microvascular regeneration and tumor progression (9,14,15). The formation of CIC structure in tumors is a functional result of active intercellular interactions within heterogeneous tumor microenvironments, which is driven by a set of core molecular elements (16,17) that are regulated by multiple factors, such as cholesterol and IL-8 (18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

Role of Heterotypic Neutrophil-in-Tumor Structure in the Prognosis of Patients With Buccal Mucosa Squamous Cell Carcinoma

et al. 2020

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Objective: To analyze the role of frequency of heterotypic neutrophil-in-tumor structure (FNiT) in the prognosis of patients with buccal mucosa squamous cell carcinoma (BMSCC). Methods: In vitro, we cocultured BMSCC cell line-H157 with neutrophils to form heterotypic neutrophil-in-tumor structures, which were then subject to fluorescence staining. Clinically, 145 patients were retrospectively enrolled. Associations between FNiT and clinicopathological variables including age, sex, smoking history, drinking history, betel nut chewing, tumor stage, node stage, metastasis, disease stage, lymphovascular invasion, extranodal extension, perineural invasion, and tumor grade were analyzed by chi-square test, and the main endpoints of interest were recurrence-free survival (RFS) and disease-specific survival (DSS) which were analyzed by the Kaplan-Meier method and Cox model. Results: Fluorescent staining results of typical heterotypic neutrophil-in-tumor structure showed that well-differentiated H157 cells had a stronger ability to internalize more neutrophils than poorly-differentiated H157 cells, with the latter often internalizing only one neutrophil or nothing. The mean FNiT was 4.2‰, with a range from 2.3‰ to 7.8‰. A total of 80 patients relapsed and 84 patients died of the disease. The 5-year RFS and DSS rate was 42% and 42%, respectively. Patients with an FNiT≥4.2‰ had a significantly higher risk for locoregional recurrence and cancer-caused death than those with an FNiT<4.2‰ (p=0.001 and p<0.001, respectively). The FNiT alone was independently significant in predicting poor RFS, and the FNiT along with tumor grade was an independent predictor for DSS. Conclusion: The FNiT as a novel predictor is significantly negatively associated with both the RFS and DSS of patients with BMSCC.

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CDKN2A inhibits formation of homotypic cell-in-cell structures

Cited by 39 publications

References 25 publications

Targeted next-generation sequencing reveals recurrence-associated genomic alterations in early-stage non-small cell lung cancer

Targeted next-generation sequencing reveals recurrence-associated genomic alterations in early-stage non-small cell lung cancer

Biological relevance of cell-in-cell in cancers

Role of Heterotypic Neutrophil-in-Tumor Structure in the Prognosis of Patients With Buccal Mucosa Squamous Cell Carcinoma

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