Mechanical Ring Interfaces between Adherens Junction and Contractile Actomyosin to Coordinate Entotic Cell-in-Cell Formation

Wang, Manna; Niu, Zubiao; Qin, Hongquan; Ruan, Banzhan; You, Zheng; Ning, Xiangkai; Gu, Songzhi; Gao, Lihua; Chen, Zhaolie; Wang, Xiaoning; Huang, Hongyan; Ma, Li; Sun, Qiang

doi:10.1016/j.celrep.2020.108071

Cited by 39 publications

(42 citation statements)

References 48 publications

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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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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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“…CIC structure is a special way of cell death with high environmental specificity that kills the internalized cells generally in an acidified lysosome-dependent way (8,18). Cell death caused by CICs is mediated by three core elements including adherens junction, contractile actomyosin and mechanical ring as well (19)(20)(21). Besides, CIC structure formation is also regulated by a set of factors, such as CDKN2a ( 22), PCDH7 (23), IL8 (24) and membrane lipids (25).…”

Section: Discussionmentioning

confidence: 99%

Subtype-Based Analysis of Cell-in-Cell Structures in Esophageal Squamous Cell Carcinoma

et al. 2021

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Cell-in-cell (CIC) structures are defined as the special structures with one or more cells enclosed inside another one. Increasing data indicated that CIC structures were functional surrogates of complicated cell behaviors and prognosis predictor in heterogeneous cancers. However, the CIC structure profiling and its prognostic value have not been reported in human esophageal squamous cell Carcinoma (ESCC). We conducted the analysis of subtyped CIC-based profiling in ESCC using “epithelium-macrophage-leukocyte” (EML) multiplex staining and examined the prognostic value of CIC structure profiling through Kaplan-Meier plotting and Cox regression model. Totally, five CIC structure subtypes were identified in ESCC tissue and the majority of them was homotypic CIC (hoCIC) with tumor cells inside tumor cells (TiT). By univariate and multivariate analyses, TiT was shown to be an independent prognostic factor for resectable ESCC, and patients with higher density of TiT tended to have longer post-operational survival time. Furthermore, in subpopulation analysis stratified by TNM stage, high TiT density was associated with longer overall survival (OS) in patients of TNM stages III and IV as compared with patients with low TiT density (mean OS: 51 vs 15 months, P = 0.04) and T3 stage (mean OS: 57 vs 17 months, P=0.024). Together, we reported the first CIC structure profiling in ESCC and explored the prognostic value of subtyped CIC structures, which supported the notion that functional pathology with CIC structure profiling is an emerging prognostic factor for human cancers, such as ESCC.

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“…During entotic CIC formation, the polarized adherens junction and contractile actomyosin are two well-established core elements 17,18 . Recently, the vinculinenriched mechanical ring was identified as a novel core element interfacing between adherens junction and actomyosin to coordinate cell internalization 19 . Besides, a group of factors, by acting on the core elements, were identified to regulate CIC formation, such as PCDH7, CDKN2A, MTRF, and LPA and the like [20][21][22][23][24][25] .…”

Section: Introductionmentioning

confidence: 99%

Role and dynamics of vacuolar pH during cell-in-cell mediated death

Ren

Tang

et al. 2021

Cell Death Dis

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The nonautonomous cell death by entosis was mediated by the so-called cell-in-cell structures, which were believed to kill the internalized cells by a mechanism dependent on acidified lysosomes. However, the precise values and roles of pH critical for the death of the internalized cells remained undetermined yet. We creatively employed keima, a fluorescent protein that displays different excitation spectra in responding to pH changes, to monitor the pH dynamics of the entotic vacuoles during cell-in-cell mediated death. We found that different cells varied in their basal intracellular pH, and the pH was relatively stable for entotic vacuoles containing live cells, but sharply dropped to a narrow range along with the inner cell death. In contrast, the lipidation of entotic vacuoles by LC3 displayed previously underappreciated complex patterns associated with entotic and apoptotic death, respectively. The pH decline seemed to play distinct roles in the two types of inner cell deaths, where apoptosis is preceded with moderate pH decline while a profound pH decline is likely to be determinate for entotic death. Whereas the cancer cells seemed to be lesser tolerant to acidified environments than noncancerous cells, manipulating vacuolar pH could effectively control inner cell fates and switch the ways whereby inner cell die. Together, this study demonstrated for the first time the pH dynamics of entotic vacuoles that dictate the fates of internalized cells, providing a rationale for tuning cellular pH as a potential way to treat cell-in-cell associated diseases such as cancer.

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Mechanical Ring Interfaces between Adherens Junction and Contractile Actomyosin to Coordinate Entotic Cell-in-Cell Formation

Cited by 39 publications

References 48 publications

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

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

Subtype-Based Analysis of Cell-in-Cell Structures in Esophageal Squamous Cell Carcinoma

Role and dynamics of vacuolar pH during cell-in-cell mediated death

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