GLI1 promotes cancer stemness through intracellular signaling pathway PI3K/Akt/NFκB in colorectal adenocarcinoma

Yang, Zheng; Zhang, Chengye; Qi, Wenbo; Cui, Yan; Xuan, Yanhua

doi:10.1016/j.yexcr.2018.10.006

Cited by 52 publications

(42 citation statements)

References 33 publications

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“…IF procedures were performed according to protocols described previously [9]. The sections were incubated with primary antibodies against TNC (1:50, Abcam, UK), anti-LSD1 (1:50, Sigma, USA) and anti-GLI1 (1:50, Sigma, USA).…”

Section: Immunofluorescence (If) Analysismentioning

confidence: 99%

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Tenascin-C predicts poor outcomes for patients with colorectal cancer and drives cancer stemness via Hedgehog signaling pathway

et al. 2020

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Background: Tenascin-C (TNC) is an extracellular matrix protein that is widely expressed in the stromal fibroblasts of various cancers. However, the roles of TNC in colorectal cancer (CRC) cells remain unclear. Methods: The expression of TNC, cancer stem cell-like (CSC) and cell cycle markers, and Hedgehog (HH) signaling pathway genes were assessed in 100 paraffin embedded clinical CRC patient tissues using immunohistochemistry. The interaction between TNC and CSC marker or HH related genes in CRC cells were detected by immunofluorescence. Cell cycle distribution was measured by flow cytometry. Migration and invasion were evaluated by transwell assays. The expressions of TNC, CSC marker, and HH related proteins were analyzed by western blot. Results: TNC expression was markedly upregulated in CRC tissues, and was associated with worse clinical outcomes. TNC overexpression was positively associated with CSC marker LSD1, cell cycle markers CDK4 and p16, and HH signaling pathway related genes SMO and GLI1 in clinical CRC tissue samples. TNC silencing downregulated the expression of the CSC marker LSD1, and the proliferation, migration, and invasion of CRC cells. Interestingly, the GLI1 inhibitor GANT61 strongly inhibited the expression of TNC in CRC cells. Conclusions: TNC may drive tumor progression and is involved in CSC properties via the HH signaling pathway. TNC has potential value in the evaluation of poor prognosis in CRC.

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Section: Immunofluorescence (If) Analysismentioning

confidence: 99%

“…All migration and invasion, and cell cycle analysis procedures were performed according to protocols described previously [9] for transfecting HT29 and HCT116 with control siRNA or TNC siRNA.…”

Section: Migration and Invasion And Cell Cycle Analysismentioning

confidence: 99%

Tenascin-C predicts poor outcomes for patients with colorectal cancer and drives cancer stemness via Hedgehog signaling pathway

et al. 2020

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“…Finally, the location of proteins in cell were observed in a confocal laser scanning microscope (Carl Zeiss, Thornwood, New York). 26…”

Section: Immunofluorescence (If) Analysismentioning

confidence: 99%

<p>Leucine Zipper-EF-Hand Containing Transmembrane Protein 1 Is a Potential Prognostic Biomarker and Promotes Cell Progression in Prostate Cancer</p>

Piao¹,

Li²,

Feng³

et al. 2020

CMAR

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The leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is a mitochondrial protein that has been associated with the occurrence and development of malignant tumors. Previous studies have shown that LETM1 expression is increased in several types of human cancer and is associated with a poor clinical outcome. However, the role of LETM1 in prostate cancer (PCa) has not yet been determined. In this study, we investigated the clinicopathological significance of LETM1 expression and its role in PCa progression. Methods: We assessed the expression of LETM1 and genes related to cancer stemness, epithelial-mesenchymal transition (EMT), cell cycle, and PI3K/Akt signaling in 133 paraffinembedded PCa tissue samples and cancer cells by using immunohistochemistry, immunofluorescence, and Western blotting. Results: LETM1 expression was significantly increased in PCa, and it was positively correlated with Gleason score, pathologic tumor (pT) stage, clinical stage, and high microvessel density. Survival analysis showed that patients with PCa with a high level of LETM1 expression exhibited a low overall survival. Cox regression analysis indicated that LETM1 is an independent poor prognostic PCa factor. Additionally, the expression of LETM1 was correlated with cancer cell stemness-associated genes, EMT-related genes, cell cycle regulatory genes, and PI3K/Akt signaling gene expression in PCa. Furthermore, knocking down LETM1 expression down-regulated the expression of stemness-related proteins, while inhibiting tumor spheroid formation, EMT-like changes, cell proliferation, migration, and invasion in PCa cells. Importantly, the PI3K inhibitor LY294002 strongly inhibited the expression of LETM1, pPI3K-p85, and pAkt (Thr308, Ser473) in PCa cells. Conclusion: These results indicate that LETM1 expression is associated with cancer cell stemness, promotes EMT-like changes and cell proliferation and is a potential prognostic biomarker for PCa.

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“…Our results showed that LY294002, a speci c PI3K inhibitor, suppressed NF-κB p65 nuclear localization, which indicates that the activation of the PI3K/AKT/NF-κB signaling cascade is regulated by AKR1B10. CyclinD1, c-myc, survivin and EMT-related proteins are downstream intracellular signal molecules for NF-κB signaling [26,31]. Thus, AKR1B10 may regulate proliferation-related and EMTrelated proteins via the PI3K/AKT/NF-κB signaling cascade.…”

Section: Discussionmentioning

confidence: 99%

AKR1B10 promotes breast cancer cell proliferation and migration via the PI3K/AKT/NF-κB signaling pathway

et al. 2020

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BackgroudAberrant expression of Aldo-Keto reductase family 1 member B10 (AKR1B10) has been observed during the progression of some human carcinomas. However, the expression pattern and clinical relevance of AKR1B10 in breast cancer (BC) need clarification.MethodsThe relationship between the high expression of AKR1B10 and the overall prognosis and disease-free survival of breast cancer patients was analyzed by Kaplan-Meier Plotter database. Breast cancer cell lines MCF-7/AKR1B10 stably overexpressing AKR1B10 and breast cancer cell lines BT-20/shAKR1B10 that knock down AKR1B10 were constructed, respectively. RT-qPCR, Western blot and immunohistochemistry were used to detect the expression of AKR1B10 in breast cancer and its normal tissues. CCK8 cell proliferation assay and cell scratch test were used to detect the proliferation and migration of breast cancer cells. Western blot was used to detect the expression of proliferation-related proteins cyclinD1, c-myc, survivin and EMT-related proteins twist, snail, slug, ZEB1, E-cadherin, PI3K, p-PI3K, AKT, p-AKT, IKBα, p-IKBα, NF-κB p65, and p-NF-κB p65 proteins in breast cancer cells. The PI3K inhibitor LY94002 was used to treat MCF-7 cells to detect PI3K/AKT/NF-κB signal cascade protein Expression, and expression of NF-κB p65 in nucleoproteins and plasma proteins.ResultsIn this study, we found that AKR1B10 expression was higher in BC tissue compared to paired non-cancerous tissue. The expression of AKR1B10 positively correlated with lymph node metastasis, tumor size, Ki67 expression, and p53 expression, but inversely correlated with overall and disease-free survival rates. Gene Ontology (GO) analysis showed that AKR1B10 was closely related to cell proliferation. Overexpression of AKR1B10 facilitated proliferation and migration of BC cells in vitro in association with induction of epithelial-mesenchymal transition. Conversely, knockdown of AKR1B10 inhibited these effects. Mechanistically, silencing AKR1B10 reduced the phosphorylation of PI3K, AKT, and NF-κB p65, whereas AKR1B10 overexpression activated these signaling molecules. Indeed, PI3K inhibition attenuated NF-κB p65 nuclear localization.ConclusionsOur results demonstrate that AKR1B10 promotes proliferation and migration of BC cells and represents a novel prognostic indicator as well as a potential therapeutic target in BC.

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GLI1 promotes cancer stemness through intracellular signaling pathway PI3K/Akt/NFκB in colorectal adenocarcinoma

Cited by 52 publications

References 33 publications

Tenascin-C predicts poor outcomes for patients with colorectal cancer and drives cancer stemness via Hedgehog signaling pathway

Tenascin-C predicts poor outcomes for patients with colorectal cancer and drives cancer stemness via Hedgehog signaling pathway

<p>Leucine Zipper-EF-Hand Containing Transmembrane Protein 1 Is a Potential Prognostic Biomarker and Promotes Cell Progression in Prostate Cancer</p>

AKR1B10 promotes breast cancer cell proliferation and migration via the PI3K/AKT/NF-κB signaling pathway

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