Molecular mechanism by which CDCP1 promotes proneural-mesenchymal transformation in primary glioblastoma

Lin, Zhiying; Zhang, Zhu; Zheng, Huanhuan; Xu, Haiyan; Wang, Yajuan; Chen, Chao; Liu, Junlu; Yi, Guozhong; Li, Zhiyong; Wang, Xiaoyan; Huang, Guanglong

doi:10.1186/s12935-021-02373-1

Cited by 6 publications

(4 citation statements)

References 77 publications

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“…Epithelial–mesenchymal transition (EMT) is a common biological process undergone during the metastasis of a variety of malignant tumor cells [ 58 , 59 ]. A malignant process similar to EMT also occurs in the evolution of GBM, called proneural–mesenchymal transition.…”

Section: Discussionmentioning

confidence: 99%

EGFRvIII Promotes the Proneural–Mesenchymal Transition of Glioblastoma Multiforme and Reduces Its Sensitivity to Temozolomide by Regulating the NF-κB/ALDH1A3 Axis

Shi

Zhai

et al. 2023

Genes

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(1) Background: Glioblastoma multiforme (GBM) is the most common and malignant intracranial tumor in adults. At present, temozolomide (TMZ) is recognized as the preferred chemotherapeutic drug for GBM, but some patients have low sensitivity to TMZ or chemotherapy resistance to TMZ. Our previous study found that GBM patients with EGFRvIII (+) have low sensitivity to TMZ. However, the reasons and possible mechanisms of the chemoradiotherapy resistance in GBM patients with EGFRvIII (+) are not clear. (2) Methods: In this study, tissue samples of patients with GBM, GBM cell lines, glioma stem cell lines, and NSG mice were used to explore the causes and possible mechanisms of low sensitivity to TMZ in patients with EGFRvIII (+)-GBM. (3) Results: The study found that EGFRvIII promoted the proneural–mesenchymal transition of GBM and reduced its sensitivity to TMZ, and EGFRvIII regulated of the expression of ALDH1A3. (4) Conclusions: EGFRvIII activated the NF-κB pathway and further regulated the expression of ALDH1A3 to promote the proneural–mesenchymal transition of GBM and reduce its sensitivity to TMZ, which will provide an experimental basis for the selection of clinical drugs for GBM patients with EGFRvIII (+).

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Section: Discussionmentioning

confidence: 99%

EGFRvIII Promotes the Proneural–Mesenchymal Transition of Glioblastoma Multiforme and Reduces Its Sensitivity to Temozolomide by Regulating the NF-κB/ALDH1A3 Axis

Shi

Zhai

et al. 2023

Genes

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“…ME2 induces the expression of MES markers, including MET, N-cadherin, YKL40, and Vimentin, while inhibiting expression of the PN gene OLIG2 ; consequently, ME2 may promote PMT in GBM 116 . In addition, CDCP1 is a transmembrane glycoprotein and a novel regulator of PMT in GBM 117 . The coding genes and their mechanisms of promoting MT are detailed in Table 1 .…”

Section: Mesenchymal Transition Regulators Of Gbmmentioning

confidence: 99%

Comprehensive understanding of glioblastoma molecular phenotypes: classification, characteristics, and transition

Xu,

Hou,

et al. 2024

Cancer Biol Med

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Among central nervous system-associated malignancies, glioblastoma (GBM) is the most common and has the highest mortality rate. The high heterogeneity of GBM cell types and the complex tumor microenvironment frequently lead to tumor recurrence and sudden relapse in patients treated with temozolomide. In precision medicine, research on GBM treatment is increasingly focusing on molecular subtyping to precisely characterize the cellular and molecular heterogeneity, as well as the refractory nature of GBM toward therapy. Deep understanding of the different molecular expression patterns of GBM subtypes is critical. Researchers have recently proposed tetra fractional or tripartite methods for detecting GBM molecular subtypes. The various molecular subtypes of GBM show significant differences in gene expression patterns and biological behaviors. These subtypes also exhibit high plasticity in their regulatory pathways, oncogene expression, tumor microenvironment alterations, and differential responses to standard therapy. Herein, we summarize the current molecular typing scheme of GBM and the major molecular/genetic characteristics of each subtype. Furthermore, we review the mesenchymal transition mechanisms of GBM under various regulators.

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“…Although rare, they have high mortality and morbidity 1 . There are four subtypes of GBM: proneural (PN), neural (NL), classical (CL), and mesenchymal (MES) 2 . Especially compared with the PN subtype, the MES subtype is more aggressive and immune-evasive, which is strongly associated with poor prognosis.…”

Section: Introductionmentioning

confidence: 99%

ALKBH5-PYCR2 Positive Feedback Loop Promotes Proneural-Mesenchymal Transition Via Proline Synthesis In GBM

Li¹,

Meng-ting²,

Pu³

et al. 2023

J. Cancer

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AlkB homolog 5, RNA demethylase (ALKBH5) is abnormally highly expressed in glioblastoma multiforme (GBM) and is negatively correlated with overall survival in GBM patients. In this study, we found a new mechanism that ALKBH5 and pyrroline-5-carboxylate reductase 2 (PYCR2) formed a positive feedback loop involved in proline synthesis in GBM. ALKBH5 promoted PYCR2 expression and PYCR2-mediated proline synthesis; while PYCR2 promoted ALKBH5 expression through the AMPK/mTOR pathway in GBM cells. In addition, ALKBH5 and PYCR2 promoted GBM cell proliferation, migration, and invasion, as well as proneural-mesenchymal transition (PMT). Furthermore, proline rescued AMPK/mTOR activation and PMT after silencing PYCR2 expression. Our findings reveal an ALKBH5-PYCR2 axis linked to proline metabolism, which plays an important role in promoting PMT in GBM cells and may be a promising therapeutic pathway for GBM.

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Molecular mechanism by which CDCP1 promotes proneural-mesenchymal transformation in primary glioblastoma

Cited by 6 publications

References 77 publications

EGFRvIII Promotes the Proneural–Mesenchymal Transition of Glioblastoma Multiforme and Reduces Its Sensitivity to Temozolomide by Regulating the NF-κB/ALDH1A3 Axis

EGFRvIII Promotes the Proneural–Mesenchymal Transition of Glioblastoma Multiforme and Reduces Its Sensitivity to Temozolomide by Regulating the NF-κB/ALDH1A3 Axis

Comprehensive understanding of glioblastoma molecular phenotypes: classification, characteristics, and transition

ALKBH5-PYCR2 Positive Feedback Loop Promotes Proneural-Mesenchymal Transition Via Proline Synthesis In GBM

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