Spindle and kinetochore-associated complex subunit 3 (SKA3) promotes stem cell-like properties of hepatocellular carcinoma cells through activating Notch signaling pathway

Bai, Shuya; Chen, Wei; Zheng, Minxue; Wang, Xiju; Wang, Peng; Zhao, Yuchong; Wang, Yun; Xiong, Si; Cheng, Bin

doi:10.21037/atm-21-1572

Cited by 7 publications

(8 citation statements)

References 45 publications

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“…Recent studies have shown that the Notch signaling pathway plays an important role in the regulation of tumor stemness by the TME. Our previous studies demonstrated that the Notch1 signaling pathway is important for promoting stem-like properties in HCC [ 27 – 29 ]. To explore the underlying mechanism by which CAF-derived STC1 promoted HCC stemness, we performed GSEA and GO analysis on the HCC samples in the TCGA database.…”

Section: Resultsmentioning

confidence: 99%

“…CSL is a ubiquitous transcription factor (TF) that regulates gene expression after recruiting other co-TFs, and its Su(H) motif largely determines the target gene of the Notch signaling pathway [ 26 ]. We and others have shown that the Notch signaling pathway is involved in cancer stemness maintenance and regulation [ 27 – 30 ]. Recent studies have found that the Notch signaling pathway also plays an important role in the regulation of cancer stemness by the TME, including in HCC [ 31 ], but its mechanism needs further exploration.…”

Section: Introductionmentioning

confidence: 99%

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The stromal-tumor amplifying STC1-Notch1 feedforward signal promotes the stemness of hepatocellular carcinoma

et al. 2023

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Background Cancer-associated fibroblasts (CAFs), an important component of the tumor microenvironment (TME), play crucial roles in tumor stemness. It has been shown in various cancer studies that stanniocalcin-1 (STC1) is secreted by CAFs, however, its function in HCC is still not clear. Methods The serum concentration and intracellular expression level of STC1 were quantified by ELISA and western blotting, respectively. The role of CAF-derived STC1 in HCC stemness was investigated by sphere formation, sorafenib resistance, colony formation, and transwell migration and invasion assays in vitro and in an orthotopic liver xenograft model in vivo. An HCC tissue microarray containing 72 samples was used to evaluate the expression of STC1 and Notch1 in HCC tissues. Coimmunoprecipitation (CoIP) and dual-luciferase reporter assays were performed to further explore the underlying mechanisms. ELISAs were used to measure the serum concentration of STC1 in HCC patients. Results We demonstrated that CAFs were the main source of STC1 in HCC and that CAF-derived STC1 promoted HCC stemness through activation of the Notch signaling pathway. In HCC patients, the expression of STC1 was positively correlated with Notch1 expression and poor prognosis. The co-IP assay showed that STC1 directly bound to Notch1 receptors to activate the Notch signaling pathway, thereby promoting the stemness of HCC cells. Our data further demonstrated that STC1 was a direct transcriptional target of CSL in HCC cells. Furthermore, ELISA revealed that the serum STC1 concentration was higher in patients with advanced liver cancer than in patients with early liver cancer. Conclusions CAF-derived STC1 promoted HCC stemness via the Notch1 signaling pathway. STC1 might serve as a potential biomarker for the prognostic assessment of HCC, and the stromal-tumor amplifying STC1-Notch1 feedforward signal could constitute an effective therapeutic target for HCC patients.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The stromal-tumor amplifying STC1-Notch1 feedforward signal promotes the stemness of hepatocellular carcinoma

et al. 2023

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“…CAFs -derived STC1 promoted HCC stemness in a Notch1-dependent manner Our previous studies have demonstrated that the Notch1 signaling pathway is important for promoting the stem-like properties in HCC [33][34][35] . To explore the underlying mechanism of how CAFs-derived STC1 promoted HCC stemness, we performed GSEA pathway enrichment analysis and GO analysis among the HCC samples in the TCGA database.…”

Section: Resultsmentioning

confidence: 99%

“…After Notch receptor activation, the Notch intracellular domain (NICD), is translocated into the nucleus and interacts with the DNA-bound protein CSL (RBP-J) to regulate the expression levels of downstream molecules [31,32] . Our previous studies have demonstrated that Notch signaling is one key signal promoting HCC stemness [33][34][35][36] .…”

Section: Introductionmentioning

confidence: 99%

The stromal-tumor amplifying STC1-Notch1 feedforward signal promotes the stemness of hepatocellular carcinoma

Bai

Zhao

Chen

et al. 2022

Preprint

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Background Cancer associated fibroblasts (CAFs), an important component of the tumor microenvironment (TME), play crucial roles in tumor stemness. Stanniocalcin-1 (STC1) was found secreted by CAFs in various cancers, but its main source and its role in hepatocellular carcinoma (HCC) was still unclear. Methods The serum and intracellular expression levels of STC1 were detected by ELISA and western blot. The role of CAFs-derived STC1 in HCC stemness was probed by sphere formation, sorafenib resistance, colony formation, and transwell migration and invasion assays in vitro and orthotopic liver xenograft tumor model in vivo. An HCC tissue microarray containing 72 samples was used to identify the STC1 and the Notch1 in HCC tissues. Co-immunoprecipitation (CoIP) and dual-luciferase reporter assay were performed to further explore the underlying mechanisms. ELISA assays were used to detect the serum concentration of STC1 in HCC patients. Results We demonstrated that CAFs were the main source of STC1 in HCC and that CAFs-derived STC1 promoted HCC stemness through the activation of the Notch signaling pathway. In HCC patients, the expression of STC1 was positively correlated with poor prognosis and the Nocth1 expression. Co-IP assay showed that STC1 directly bound to Notch1 receptors to activate the Notch signaling pathway, thereby promoting the stemness of HCC. Our data further demonstrated that STC1 was a direct transcriptional target of CSL in HCC cells. Furthermore, ELISA revealed that the serum STC1 concentration was higher in patients with advanced liver cancer than patients with early liver cancer. Conclusions CAFs-derived STC1 promoted HCC stemness via the Notch signaling pathway. STC1 might serve as a potential biomarker for the prognostic assessment of HCC, and the stromal-tumor amplifying STC1-Notch1 feedforward signal could provide an effective therapeutic target for HCC patients.

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“…In vitro and in vivo experiments have demonstrated that the downregulation of SKA3 significantly inhibits cell proliferation, induces cell cycle arrest in G1-S phase and suppresses tumorigenesis. On the other hand, the overexpression of SKA3 increased migration, invasion, proliferation, self-renewal, Sorafenib resistance, and tumorigenic abilities of HCC cells 54 , 56 , 58 . Mechanistically (Fig.…”

Section: Role Of Ska3 In Human Cancermentioning

confidence: 96%

SKA3 targeted therapies in cancer precision surgery: bridging bench discoveries to clinical applications – review article

Feng,

Wang,

Xiao

et al. 2024

International Journal of Surgery

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Spindle and kinetochore-associated complex subunit 3 (SKA3) is a microtubule-binding subcomplex of the outer kinetochore which plays a vital role in proper chromosomal segregation and cell division. Recently, SKA3 have been demonstrated its oncogenic role of tumorigenesis and development in cancers. In this review, we comprehensively deciphered SKA3 in human cancer from various aspects, including bibliometrics, pan-cancer analysis and narrative summary. We also provided top 10 predicted drugs targeting SKA3. We proposed that SKA3 was a potential target and brought new therapeutic opportunities for cancer patients.

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Spindle and kinetochore-associated complex subunit 3 (SKA3) promotes stem cell-like properties of hepatocellular carcinoma cells through activating Notch signaling pathway

Cited by 7 publications

References 45 publications

The stromal-tumor amplifying STC1-Notch1 feedforward signal promotes the stemness of hepatocellular carcinoma

The stromal-tumor amplifying STC1-Notch1 feedforward signal promotes the stemness of hepatocellular carcinoma

The stromal-tumor amplifying STC1-Notch1 feedforward signal promotes the stemness of hepatocellular carcinoma

SKA3 targeted therapies in cancer precision surgery: bridging bench discoveries to clinical applications – review article

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