Single-cell RNA-seq recognized the initiator of epithelial ovarian cancer recurrence

Kan, Tongtong; Zhang, Shupeng; Zhou, Shengtao; Zhang, Ya; Zhao, Yun; Gao, Yan; Zhang, Tao; Gao, Feng; Wang, Xin; Zhao, Linjie; Yang, Mengsu

doi:10.1038/s41388-021-02139-z

Cited by 36 publications

(28 citation statements)

References 47 publications

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“…Epithelial ovarian cancer (EOC) is the main pathological subtype, it is still the most lethal gynecological cancer, accounting for more than 95% of ovarian malignancies. Although epithelial ovarian cancers (EOCs) are sensitive to chemotherapy, however, patients frequently develop recurrent disease following initial platinum-taxane chemotherapy [1][2][3]. Tumor metastasis is closely associated with poor prognosis and is also the main cause of death in patients with ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

Hexokinase 2 promoted cell motility and proliferation by activating Akt1/p-Akt1 in human ovarian cancer cells

et al. 2022

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Background Recently, increasing evidence has indicated that elevation of Hexokinase 2 (HK2) plays an important role in several cancers on regulating cell motility and growth. However, its role on regulating cell EMT in human ovarian cancer still less to known. Methods The transwell and wound-healing assay were used to detect the effective of HK2 on regulating motility of ovarian cancer cells. Real Time PCR and Western Blotting were used to explore the changing of EMT-related proteins in HK2-modified cells. The clonogenic formation, cell growth curves and MTT assays were used to evaluate the effective of HK2 on regulating cell proliferation in HK2-modified cells. The flow cytometry was used to detect the differences in the distribution of cells in the cell cycle between the HK2-modified cells and their control cells. The correlation of HK2 and Akt1/p-Akt1 was explored by using Western Blotting, Akt1 inhibitor (MK2206) and transient transfection of an Akt1 recombinant plasmid. The potential correlation between HK2 and EMT-related proteins in human ovarian cancer tissues and OV (ovarian serous cystadenocarcinoma) was confirmed by using Pearson correlation analysis and TIMER 2.0. Results In ovarian cancer cells, overexpressing of HK2 enhanced cell motility by inducing of EMT-related proteins, such as CDH2, fibronectin, MMP9, ZEB1, ZEB2 and vimentin. Moreover, overexpressing of HK2 promoted cell growth by reducing p21 and p27 expression in ovarian cancer cells. Further studies demonstrated that this promotion of cell motility and growth by HK2 was probably a result of it activating of Akt1 (p-Akt1) in ovarian cancer cells. Additionally, the positive correlation between HK2 and p-Akt1, fibronectin, MMP9 expression in human ovarian cancer samples was verified by using Pearson correlation analysis. The positive correlation between HK2 and CDH2, fibronectin, MMP9, ZEB1, ZEB2 and vimentin in OV (ovarian serous cystadenocarcinoma) was confirmed by using TIMER 2.0. Conclusion This study demonstrated that HK2 could induce EMT-related proteins and reduce cell cycle inhibitor by activating Akt1 in human ovarian cancer cells, subsequently enhancing cell motility and growth, suggesting that HK2 participate in the malignant process of ovarian cancer by interacting with Akt1.

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Section: Introductionmentioning

confidence: 99%

Hexokinase 2 promoted cell motility and proliferation by activating Akt1/p-Akt1 in human ovarian cancer cells

et al. 2022

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“…Strikingly, however, HGSOC populations post-neoadjuvant chemotherapy were enriched for a stress-associated profile (see Table 2) [56]. Pools of HGSOC cells with a similar stress profile have also been identified as likely sources of relapse-initiating cells [57]. These are two examples of robust studies which were able to differentiate between refractory and resistant HGSOC populations by following the genesis and trajectory of resistanceassociated profiles before and after treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Kan et al similarly identified that relapseinitiating HGSOC cells can largely originate from a subpopulation early in tumorigenesis with a high-stress signature. Relapse-initiating cells also developed over the course of HGSOC progression [57]. By identifying the intrinsically resistant populations in refractory HGSOC, subsequent chemotherapeutic interventions can be designed and optimized to target known vulnerabilities of these distinct populations.…”

Section: Chemorefractory Hgsoc Highlights the Priming Capabilities Of...mentioning

confidence: 99%

Comparing the Secretomes of Chemorefractory and Chemoresistant Ovarian Cancer Cell Populations

Lee

Pena

Dawson

2022

Cancers

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High-grade serous ovarian cancer (HGSOC) constitutes the majority of all ovarian cancer cases and has staggering rates of both refractory and recurrent disease. While most patients respond to the initial treatment with paclitaxel and platinum-based drugs, up to 25% do not, and of the remaining that do, 75% experience disease recurrence within the subsequent two years. Intrinsic resistance in refractory cases is driven by environmental stressors like tumor hypoxia which alter the tumor microenvironment to promote cancer progression and resistance to anticancer drugs. Recurrent disease describes the acquisition of chemoresistance whereby cancer cells survive the initial exposure to chemotherapy and develop adaptations to enhance their chances of surviving subsequent treatments. Of the environmental stressors cancer cells endure, exposure to hypoxia has been identified as a potent trigger and priming agent for the development of chemoresistance. Both in the presence of the stress of hypoxia or the therapeutic stress of chemotherapy, cancer cells manage to cope and develop adaptations which prime populations to survive in future stress. One adaptation is the modification in the secretome. Chemoresistance is associated with translational reprogramming for increased protein synthesis, ribosome biogenesis, and vesicle trafficking. This leads to increased production of soluble proteins and extracellular vesicles (EVs) involved in autocrine and paracrine signaling processes. Numerous studies have demonstrated that these factors are largely altered between the secretomes of chemosensitive and chemoresistant patients. Such factors include cytokines, growth factors, EVs, and EV-encapsulated microRNAs (miRNAs), which serve to induce invasive molecular, biophysical, and chemoresistant phenotypes in neighboring normal and cancer cells. This review examines the modifications in the secretome of distinct chemoresistant ovarian cancer cell populations and specific secreted factors, which may serve as candidate biomarkers for aggressive and chemoresistant cancers.

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“…To prevent or to overcome resistance, we need to implement more accurate molecular profiling techniques. Single‐cell technologies are able to dissect ITH at the scale of individual tumour cells, revealing rare subpopulations and enhancing our understanding of drug resistance and relapse [ 176 , 177 ]. In this context, the development of single‐cell RNA‐seq (scRNA‐seq) technologies has been seen as a new stepping stone towards an increased understanding of cancer biology.…”

Section: Targeting Tumour Heterogeneity: Ith and D...mentioning

confidence: 99%

Bioinformatics roadmap for therapy selection in cancer genomics

et al. 2022

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Single-cell RNA-seq recognized the initiator of epithelial ovarian cancer recurrence

Cited by 36 publications

References 47 publications

Hexokinase 2 promoted cell motility and proliferation by activating Akt1/p-Akt1 in human ovarian cancer cells

Hexokinase 2 promoted cell motility and proliferation by activating Akt1/p-Akt1 in human ovarian cancer cells

Comparing the Secretomes of Chemorefractory and Chemoresistant Ovarian Cancer Cell Populations

Bioinformatics roadmap for therapy selection in cancer genomics

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