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The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.

EGFR/SRC/ERK-stabilized YTHDF2 promotes cholesterol dysregulation and invasive growth of glioblastoma

Open access
Fang, Runping, Chen, Xin, Zhang, Sicong, Shi, Hui, Ye, Youqiong, Shi, Hailing, Zou, Zhongyu, Li, Peng, Guo, Qing, Ma, Li, He, Chuan, Huang, Suyun·2021·Nature Communications

Abstract

Glioblastoma (GBM) is the most common type of adult malignant brain tumor, but its molecular mechanisms are not well understood. In addition, the knowledge of the disease-associated expression and function of YTHDF2 remains very limited. Here, we show that YTHDF2 overexpression clinically correlates with poor glioma patient prognosis. EGFR that is constitutively activated in the majority of GBM causes YTHDF2 overexpression through the EGFR/SRC/ERK pathway. EGFR/SRC/ERK signaling phosphorylates YTHDF2 serine39 and threonine381, thereby stabilizes YTHDF2 protein. YTHDF2 is required for GBM cell proliferation, invasion, and tumorigenesis. YTHDF2 facilitates m 6 A-dependent mRNA decay of LXRA and HIVEP2, which impacts the glioma patient survival. YTHDF2 promotes tumorigenesis of GBM cells, largely through the downregulation of LXRα and HIVEP2. Furthermore, YTHDF2 inhibits LXRα-dependent cholesterol homeostasis in GBM cells. Together, our findings extend the landscape of EGFR downstream circuit, uncover the function of YTHDF2 in GBM tumorigenesis, and highlight an essential role of RNA m 6 A methylation in cholesterol homeostasis.

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Metadata

Authors
Fang, R., Chen, X., Zhang, S., Shi, H., Ye, Y., Shi, H., Zou, Z., Li, P., Guo, Q., Ma, L., He, C., & Huang, S.
Venue
Nature Communications
Published
2021-01-08
Volume
12
Issue
1
Pages
177-177
ISSN
2041-1723 (ISSN-L)
OpenAlex
W3118401914
Cited by
312
References
10
FWCI
15.63
Type
journal article
Language
en
Open access
gold

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