Overexpression of TELO2 decreases survival in human high-grade gliomas

Feng, Shao-Wei; Chen, Ying; Tsai, Wen‐Chiuan; Chiou, Hsin-Ying Clair; Wu, Sheng‐Tang; Huang, Li‐Chun; Lin, Chin; Hsieh, Chih-Chuan; Yang, Yu-Chih; Hueng, Dueng‐Yuan

doi:10.18632/oncotarget.10021

Cited by 6 publications

(7 citation statements)

References 32 publications

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“…The differential expression of TELO2 during the various stages of CRC offset its role in the prognosis suggesting that TELO2 plays a distinctive role in the development of CRC. The role of TELO2 in the prognosis of CRC, which differs from that in breast cancer (14), is still unclear, indicating that mechanism of TELO2 is different in various cancers. Next, we needed to confirm the mechanism of TELO2-induced cancer progression in CRC.…”

Section: Discussionmentioning

confidence: 99%

“…Degradation of TELO2 promotes the survival of multiple myeloma under growth factor withdrawal ( 12 ). Although there are several reports indicating that TELO2 demonstrates an oncogenic profile in solid tumors, such as breast cancer ( 13 ) and high-grade gliomas ( 14 ), the role and molecular mechanism of TELO2 in CRC tumorigenesis have yet to be defined. A study on TELO2 in CRC demonstrates that a germline mutation of TELO2 regulated the senescence pathway and is related to sessile serrated adenomas and adenocarcinoma progression ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

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TELO2 induced progression of colorectal cancer by binding with RICTOR through mTORC2

et al. 2020

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Colorectal cancer (CRC) is a common cancer worldwide, and its treatment strategies are limited. The underlying mechanism of CRC progression remains to be determined. Telomere maintenance 2 (TELO2) is a mTOR-interacting protein. Both the role and molecular mechanism of TELO2 in cancer progression remain unknown. In this study, the gene expression database of normal and tumor tissue, in addition to western blot analysis, and immunohistochemistry (IHC) were used to determine the expression and location of TELO2 in CRC and normal tissues. Clinical features of a tissue array were collected and analyzed. WST-1, soft agar, flow cytometry, wound healing, and invasion assays were employed to verify the role of TELO2 in the growth, cell cycle, migration, and invasion of CRC cells. The correlation between TELO2 and RICTOR (rapamycin-insensitive companion of mTOR) was analyzed by bioinformatics, IHC, and immunoprecipitation. Normal and serum-deprived cells were collected to detect the protein level of TELO2 and its downstream effectors. The results revealed that TELO2 was significantly upregulated in CRC, and TELO2 inhibition significantly restrained the growth, cell cycle, and metastasis of CRC cells. TELO2 overexpression correlated with age, lymph node metastasis, and TNM stage of CRC patients. In addition, TELO2 was positively correlated with RICTOR in CRC and induced tumor progression mainly via RICTOR with serum in culture. RICTOR induced the degradation of TELO2 upon serum deprivation in an mTOR-independent manner. These findings indicate that TELO2 promotes tumor progression via RICTOR in a serum-dependent manner, which may be a potential therapeutic target for CRC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TELO2 induced progression of colorectal cancer by binding with RICTOR through mTORC2

et al. 2020

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“…Our previous study demonstrated that human high-grade gliomas show increased TELO2 mRNA expression and that the overexpression of TELO2 mRNA correlates with shorter survival outcomes, suggesting that TELO2 is an oncogene in human gliomas [16]. Here, we tried to figure out the oncogenic role of TELO2 in tumorigenesis.…”

Section: Resultsmentioning

confidence: 99%

“…TELO2 is not only critical for protein stability, but it is also essential for the integrity of mTOR complexes. Many studies have shown that TELO2 might play an oncogene role in solid tumors [11,[16][17][18]. Our previous study showed that Figure 8.…”

Section: Discussionmentioning

confidence: 97%

“…Many studies have revealed that TELO2 might be an oncogenic protein in solid tumors, such as breast cancer and high-grade gliomas [8,11,[16][17][18]. Our previous study showed that human high-grade gliomas increase TELO2 mRNA expression and that overexpression of TELO2 mRNA expression correlates with shorter survival outcomes, supporting the finding that TELO2 is an oncogene in human gliomas [16]. Grade III anaplastic astrocytoma and grade IV glioblastoma multiforme (GBM) are both defined as high-grade gliomas with poor survival outcomes by the World Health Organization (WHO) [19,20].…”

Section: Introductionmentioning

confidence: 99%

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Exploring the Functional Roles of Telomere Maintenance 2 in the Tumorigenesis of Glioblastoma Multiforme and Drug Responsiveness to Temozolomide

Feng

Chiu

et al. 2023

IJMS

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Glioblastoma multiforme (GBM) is a grade IV human glioma. It is the most malignant primary central nervous system tumor in adults, accounting for around 15% of intracranial neoplasms and 40–50% of all primary malignant brain tumors. However, the median survival time of GBM patients is still less than 15 months, even after treatment with surgical resection, concurrent chemoradiotherapy, and adjuvant chemotherapy with temozolomide (TMZ). Telomere maintenance 2 (TELO2) mRNA is highly expressed in high-grade glioma patients, and its expression correlates with shorter survival outcomes. Hence, it is urgent to address the functional role of TELO2 in the tumorigenesis and TMZ treatment of GBM. In this study, we knocked down TELO2 mRNA in GBM8401 cells, a grade IV GBM, compared with TELO2 mRNA overexpression in human embryonic glial SVG p12 cells and normal human astrocyte (NHA) cells. We first analyzed the effect of TELO2 on the Elsevier pathway and Hallmark gene sets in GBM8401, SVG p12, and NHA via an mRNA array analysis. Later, we further examined and analyzed the relationship between TELO2 and fibroblast growth factor receptor 3, cell cycle progression, epithelial–mesenchymal transient (EMT), reactive oxygen species (ROS), apoptosis, and telomerase activity. Our data showed that TELO2 is involved in several functions of GBM cells, including cell cycle progression, EMT, ROS, apoptosis, and telomerase activity. Finally, we examined the crosstalk between TELO2 and the responsiveness of TMZ or curcumin mediated through the TELO2–TTI1–TTI2 complex, the p53-dependent complex, the mitochondrial-related complex, and signaling pathways in GBM8401 cells. In summary, our work provides new insight that TELO2 might modulate target proteins mediated through the complex of phosphatidylinositol 3-kinase-related kinases in its involvement in cell cycle progression, EMT, and drug response in GBM patients.

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Advances on the Structure of the R2TP/Prefoldin-like Complex

Muñoz-Hernández

Pal

Rodríguez

et al. 2018

Advances in Experimental Medicine and Biology

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Cellular stability, assembly and activation of a growing list of macromolecular complexes require the action of HSP90 working in concert with the R2TP/Prefoldinlike (R2TP/PFDL) co-chaperone. RNA polymerase II, snoRNPs and complexes of PI3kinase-like kinases, a family that includes the ATM, ATR, DNA-PKcs, TRAPP, SMG1 and mTOR proteins, are among the clients of the HSP90-R2TP system. Evidence links the R2TP/PFDL pathway with cancer, most likely because of the essential role in pathways commonly deregulated in cancer. R2TP forms the core of the co-cochaperone and orchestrates the recruitment of HSP90 and clients, whereas prefoldin and additional prefoldin-like proteins, including URI, associate with R2TP, but their function is still unclear. The mechanism by which R2TP/PFLD facilitates assembly and activation of such a variety of macromolecular complexes is poorly understood. Recent efforts in the structural characterization of R2TP have started to provide some mechanistic insights. We summarize recent structural findings, particularly how cryo-electron microscopy (cryo-EM) is contributing to our understanding of the architecture of the R2TP core complex. Structural differences discovered between yeast and human R2TP reveal unanticipated complexities of the metazoan R2TP complex, and opens new and interesting questions about how R2TP/PFLD works.

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Overexpression of TELO2 decreases survival in human high-grade gliomas

Cited by 6 publications

References 32 publications

TELO2 induced progression of colorectal cancer by binding with RICTOR through mTORC2

TELO2 induced progression of colorectal cancer by binding with RICTOR through mTORC2

Exploring the Functional Roles of Telomere Maintenance 2 in the Tumorigenesis of Glioblastoma Multiforme and Drug Responsiveness to Temozolomide

Advances on the Structure of the R2TP/Prefoldin-like Complex

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