API5 confers cancer stem cell-like properties through the FGF2-NANOG axis

Song, Kwon Ho; Cho, H; Kim, S; Lee, H J; Oh, Se Jin; Woo, Seon Rang; Hong, Soon Oh; Jang, H S; Noh, Kyung Hee; Choi, Chel Hun; Chung, Joon‐Yong; Hewitt, Stephen M.; Kim, J H; Son, Moeun; Kim, Seok Ho; Lee, B I; Park, H C; Bae, Young-Ki; Kim, T W

doi:10.1038/oncsis.2016.87

Cited by 29 publications

(26 citation statements)

References 29 publications

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“…There are reports that E2F1 is upregulated during the carcinogenesis of breast cancer [ 28 ]. It was found to be involved in Nanog expression in breast cancer [ 29 ]. In this study, dual-luciferase reporter assay confirmed the existence of the regulatory pathway LINC00511/miR-185-3p/E2F1.…”

Section: Discussionmentioning

confidence: 99%

[Retracted] LINC00511 Promotes Osteosarcoma Tumorigenesis and Invasiveness through the miR‐185‐3p/E2F1 Axis

Chen

Zhang

et al. 2020

BioMed Research International

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Osteosarcoma is a malignant tumor that seriously threatens human health. Numerous studies have pointed out the potential of long noncoding RNAs (lncRNAs) as new therapeutic targets for various human cancers. Therefore, we mainly investigate whether there is a new type of lncRNA pathway involved in regulating the development of osteosarcoma. The present study shows the higher expression levels of LINC00511 correlates to a shorter overall survival and disease-free survival time in patients with sarcoma. It is significantly higher in the clinical samples of osteosarcoma patients than in normal adjacent cancer tissues. We used U373 and SW1353 osteosarcoma cells to determine the effect of lncRNA on osteosarcoma proliferation and invasion by knocking down LINC00511 compared with controls. The results showed that the LINC00511 knockdown significantly suppressed osteosarcoma cell growth and metastasis. To explore the mechanisms of LINC00511 in osteosarcoma, we tested whether LINC00511 could competitively stimulate miR-185-3p and regulate E2F1 as a ceRNA. The results showed that LINC00511 knockdown induced the increased level of miR-185-3p levels; however, miR-185-3p overexpression suppressed LINC00511 levels. In addition, the results also demonstrated that LINC00511 knockdown or miR-185-3p overexpression could reduce E2F1 levels in osteosarcoma cells. The dual-luciferase reporter assay verified the direct interaction between miR-185-3p and LINC00511 or E2F1. These results may offer an explanation of how the lncRNA affects the progression of osteosarcoma, and our study shows that LINC00511 can be a novel biomarker in osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

[Retracted] LINC00511 Promotes Osteosarcoma Tumorigenesis and Invasiveness through the miR‐185‐3p/E2F1 Axis

Chen

Zhang

et al. 2020

BioMed Research International

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“…Strong IFN-γ response to a wildtype as well as mutated peptide sequence derived from apoptotic inhibitor 5 (API5) were observed in TIL from patient GBM-A. The abrogation of API5 protein expression in human cervical cancer cells has been implicated in tumor regression and sensitivity to chemotherapy [ 19 ]. Patient GBM-C had TILs which responded with TNF-α production to a mutated peptide provided by the transforming growth factor beta regulator 4 (TBRG4), which is involved in cell growth and proliferation via the transforming growth factor beta (TGF-β) signaling pathway.…”

Section: Resultsmentioning

confidence: 99%

Identification of neoepitopes recognized by tumor-infiltrating lymphocytes (TILs) from patients with glioma

et al. 2018

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Neoepitope-specific T-cell responses have been shown to induce durable clinical responses in patients with advanced cancers. We explored the recognition patterns of tumor-infiltrating T lymphocytes (TILs) from patients with glioblastoma multiforme (GBM), the most fatal form of tumors of the central nervous system. Whole-genome sequencing was used for generating DNA sequences representing the entire spectrum of ‘private’ somatic mutations in GBM tumors from five patients, followed by 15-mer peptide prediction and subsequent peptide synthesis. For each mutated peptide sequence, the wildtype sequence was also synthesized and individually co-cultured with autologous GBM TILs, which had been expanded in vitro with a combination of interleukin (IL)-2, IL-15 and IL-21. After seven days of culture, interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α) and/or IL-17A production was measured by ELISA in culture supernatants, and used as an epitope-specific immune response readout. Mutated peptides that induced a strong cytokine response were considered to contain legitimate neoepitopes. TILs from 5/5 patients with GBM exhibited specific immune reactivity profiles to the nominal target peptides, defined by IFN-γ and/or TNF-α production, as well as IL-17A. Neoepitopes, defined by mutated peptides inducing IFN-γ and/or TNF-α production without or only minimal reactivity to the wildtype sequences, were found for each individual patient. CD8+ TILs dominated the patients’ responses to private neoepitopes. The present study shows that neoepitope-specific TIL reactivity constitutes an important arm of anti-tumor immune responses in patients with GBM, and thus a powerful tool for developing next-generation personalized immunotherapies.

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“…1c), indicating a crucial role of HSP90A in a tumor-intrinsic resistance to CTL. Besides immune resistance, we reported the P3 cells have multi-modal resistance to chemotherapy and radiotherapy, and cancer stem cell (CSC)-like property 8,23,24 . Notably, siHSP90AA1 transfection re-sensitized P3 cells to chemotherapy and radiotherapy ( Fig.…”

Section: Resultsmentioning

confidence: 99%

HSP90A inhibition promotes anti-tumor immunity by reversing multi-modal resistance and stem-like property of immune-refractory tumors

Song

Kim

et al. 2020

Nat Commun

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Cancer immunotherapy has emerged as a promising cancer treatment. However, the presence of immune-refractory tumor cells limits its clinical success by blocking amplification of anti-tumor immunity. Previously, we found that immune selection by immunotherapy drives the evolution of tumors toward multi-modal resistant and stem-like phenotypes via transcription induction of AKT co-activator TCL1A by NANOG. Here, we report a crucial role of HSP90A at the crossroads between NANOG-TCL1A axis and multi-aggressive properties of immune-edited tumor cells by identifying HSP90AA1 as a NANOG transcriptional target. Furthermore, we demonstrate that HSP90A potentiates AKT activation through TCL1Astabilization, thereby contributing to the multi-aggressive properties in NANOG high tumor cells. Importantly, HSP90 inhibition sensitized immune-refractory tumor to adoptive T cell transfer as well as PD-1 blockade, and re-invigorated the immune cycle of tumor-reactive T cells. Our findings implicate that the HSP90A-TCL1A-AKT pathway ignited by NANOG is a central molecular axis and a potential target for immune-refractory tumor.

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API5 confers cancer stem cell-like properties through the FGF2-NANOG axis

Cited by 29 publications

References 29 publications

[Retracted] LINC00511 Promotes Osteosarcoma Tumorigenesis and Invasiveness through the miR‐185‐3p/E2F1 Axis

[Retracted] LINC00511 Promotes Osteosarcoma Tumorigenesis and Invasiveness through the miR‐185‐3p/E2F1 Axis

Identification of neoepitopes recognized by tumor-infiltrating lymphocytes (TILs) from patients with glioma

HSP90A inhibition promotes anti-tumor immunity by reversing multi-modal resistance and stem-like property of immune-refractory tumors

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