Different p53 genotypes regulating different phosphorylation sites and subcellular location of CDC25C associated with the formation of polyploid giant cancer cells

Li, Kai; Zheng, Minying; Zhao, Qi; Zhang, Kexin; Li, Zugui; Fu, Fangmei; Zhang, Hao; Du, Jiaxing; Li, Yuwei

doi:10.1186/s13046-020-01588-w

Cited by 25 publications

(38 citation statements)

References 40 publications

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“…Plate clone formation experiment was used to evaluate the proliferation ability of MDA-MB-231 and BT-549 cells transfected with and without miRNA inhibitors, mimics and performed as described previously (Liu et al, 2020 ). The detailed information is provided in Supplementary Materials and Methods .…”

Section: Methodsmentioning

confidence: 99%

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Clinicopathological Significances of Cancer Stem Cell-Associated HHEX Expression in Breast Cancer

Zhang

Zhao

et al. 2020

Front. Cell Dev. Biol.

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Aberrant expression of the transcription factor hematopoietic ally expressed homeobox/proline-rich homeodomain (HHEX/PRH) is implicated in numerous cancers. However, the association of HHEX with breast cancer (BC) remains unclear. In this study, HHEX mRNA and protein expression were analyzed using the Oncomine, UALCAN, GEPIA, TCGAportal, and HPA databases. We evaluated the effect of HHEX on clinicopathological parameters using Kaplan–Meier plotter, OncoLnc, TCGAportal, PROGgeneV2, and BC-GenExMiner. Western blotting was performed to compare the level of HHEX in breast samples of Tientsin Albino 2 mice, human breast precancerous lesions, benign breast tumors, and BC. The correlation between HHEX and cancer stem cells was investigated using the GEO (GSE52327 and GSE94865) and GEPIA datasets. Networks between HHEX and survival-related gene marker sets and microRNAs were analyzed using GEPIA, StarBase, and Cytoscape. Results of this study showed that HHEX expression in BC was significantly lower than those in breast precancerous lesions and benign breast tumors at both mRNA and protein levels. BC patients with lower HHEX expression had significantly worse overall survival and disease-free survival. Moreover, HHEX significantly affected the clinicopathology of BC. Specifically, low HHEX expression was correlated with the following groups of patients: age ≤51 years, ER-negative or PR-negative patients, HER-2 positive, triple-negative breast cancer, and basal-like BC. Immunohistochemical analysis of the breast samples showed significant differences of HHEX staining index (P < 0.001) among the three groups. To further investigate the mechanism, we determined the intersection of differentially expressed genes related to BC stem cells and those genes after HHEX expression was altered. This led to the identification of four potentially regulated genes-CXL12, BLNK, PAG1, and LPXN. Using StarBase and km-plotter, the negative regulation of HHEX expression and survival trends, including miR-130b, miR-30e, and miR-301b were joined into miRNA-HHEX-mRNA potential regulatory network. The abilities of proliferation, migration and invasion increased in MDA-MB-231 and BT-549 breast cancer cell lines after HHEX down expression and decreased after HHEX overexpression compared them in the control cells. In conclusion, these data suggest that HHEX expression is downregulated in BC and HHEX may regulate the development of BC through the stem cell-related genes.

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Section: Methodsmentioning

confidence: 99%

“…IHC staining was carried out as described previously (Liu et al, 2020 ). The detailed information of staining, scoring, and quantification had been described in the Supplementary Materials and Methods .…”

Section: Methodsmentioning

confidence: 99%

Clinicopathological Significances of Cancer Stem Cell-Associated HHEX Expression in Breast Cancer

Zhang

Zhao

et al. 2020

Front. Cell Dev. Biol.

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“…The abilities of cell migration and invasion assay were evaluated as previously described [11] and detailed information about these assays were provided in the Supplementary Materials and Methods.…”

Section: Cell Migration and Invasion Assaysmentioning

confidence: 99%

SUMOylation of S100A10 promotes its nuclear localization and enhances the migration and invasion of PGCCs and their daughter cells

Zhao¹,

Zhang²,

Li³

et al. 2021

Preprint

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Background Our previous studies have confirmed that cobalt chloride (CoCl2) or chemoradiotherapy could induce the formation of polyploid tumor giant cells (PGCCs) and daughter cells derived from PGCCs had strong proliferation and migration abilities. However, the detailed molecular mechanism is unclear. Methods Cell functional experiments, co-immunoprecipitation, MG132 and ginkgolic acid treatment, western blot, and ChiP-Seq were used to identify the mechanism of S100A10 nuclear location. Results CoCl2 was used to induce the formation of PGCCs in LoVo and HCT116 CRC cells. The proliferation and migration abilities of PGCCs and their daughter cells decreased significantly after S100A10 knockdown. In the control cells, S100A10 was mainly ubiquitinated, while in PGCCs and daughter cells, S100A10 was mainly SUMOylated, which was associated with S100A10 nuclear location. After SUMO1 was inhibited, the nuclear S100A10 in PGCCs and daughter cells decreased, and their proliferation and migration abilities significantly decreased. ChiP-Seq combined with real-time fluorescent quantitative PCR showed that S100A10 regulated the expression of neutrophil defensin 3 (DEFA3), receptor-type tyrosine-protein phosphatase N2 (PTPRN2), and rho guanine nucleotide exchange factor 18 (ARHGEF18). The expression of S100A10 in the nuclei and cytoplasm of rectal cancer after neoadjuvant chemoradiation (nCRT) and liver metastases increased compared with that in rectal cancer without nCRT. Conclusion The expression and nuclear localization of S100A10 modified by SUMOylation were associated with the high proliferation and migration of PGCCs and their daughter cells, and the differentiation, metastases, and relapse of CRCs by regulating the expression of ARHGEF18, PTPRN2, and DEFA3.

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“…IHC staining was carried out as described previously (Liu et al, 2020). The detailed information of staining, scoring, and quantification had been described in the Supplementary Materials and Methods.…”

Section: Immunohistochemical Staining Scoring and Quantificationmentioning

confidence: 99%

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Different p53 genotypes regulating different phosphorylation sites and subcellular location of CDC25C associated with the formation of polyploid giant cancer cells

Cited by 25 publications

References 40 publications

Clinicopathological Significances of Cancer Stem Cell-Associated HHEX Expression in Breast Cancer

Clinicopathological Significances of Cancer Stem Cell-Associated HHEX Expression in Breast Cancer

SUMOylation of S100A10 promotes its nuclear localization and enhances the migration and invasion of PGCCs and their daughter cells

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