NGDC - GSA for Human

HRA001603

HRA001603.xlsx

Title:

PHLDB2 mediates cetuximab resistance via interacting with EGFR in latent metastasis of colorectal cancer

Release date:

2021-11-29

Description:

Latent metastasis of colorectal cancer (CRC) frequently develops months or years after primary surgery followed by adjuvant therapies and may progress rapidly even with targeted therapy administered, but the underlying mechanism remain unclear. Here, we performed transcriptional profiling of paired primary and metastatic tumor samples and identified PHLDB2 as a potential regulator in latent liver metastasis. Detailed mechanistic study revealed that chemotherapeutic agents-induced oxidative stress promotes METTL14-mediated m6A modification of PHLDB2 mRNA, facilitating its protein expression. Upregulated PHLDB2 stabilizes EGFR and promotes its nuclear translocation, which in turn results in EGFR signaling activation and consequent cetuximab resistance. Moreover, Arg1163 (R1163) of PHLDB2 is crucial for interaction with EGFR, and R1163A mutation abrogates its regulatory function in EGFR signaling.

Data Accessibility:

Controlled access Request Data

BioProject:

PRJCA007055

Study type:

Disease Study

Disease name:

colorectal adenocarcinoma

Data Access Committee

For each controlled access study, there is a corresponding Data Access Committee(DAC) to determine the access permissions. Access to actual data files is not managed by NGDC.

DAC NO.:

HDAC000201

DAC name:

SKLB-xuheng

Contact person:

Xu Heng

Email:

xuheng81916@scu.edu.cn

Description:

xu heng lab from state key laboratory of biotherapy

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