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| Status |
Public on Jul 02, 2019 |
| Title |
Knock down of MTHFD2 of lung adenocarcinoma cell line H322 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Lung cancer is leading cause of cancer-related death in the world, because of high recurrence rate and acquired resistance to targeting drugs such as gefitinib. Here we uncover a critical MTHFD2 enzyme-mediated purine synthesis pathway in mitochondria in poor prognostic lung cancer. Expression of MTHFD2 was induced by epidermal growth factor (EGF) stimulation. It was overexpressed in gefitinib-resistant cancer cells and high-grade tumor tissues. Knockdown of MTHFD2 significantly decreased not only in vitro and in vivo cell growth but also tumor sphere formation and tumor initiating activity, properties of cancer stem-like cells. Integrated analysis of metabolome and transcriptome of MTHFD2 knocked-down cells revealed significant accumulation of the nucleotide intermediates before MTHFD2-mediated one carbon transfer and marked deficiency of purine nucleotides required for cell growth. Thus we provide evidence that MTHFD2 pathway is critical for growth of both cancer cells and cancer stem-like cells as an Achilles heel to eradicate tumors in poor prognostic lung cancer.
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| Overall design |
Comaprison between negative control cells and MTHFD2 knocked down cells. There are three biological replicates for each conditions.
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| Contributor(s) |
Nishimura T, Nakata A, Meguro-Horike M, Horike S, Saitoh K, Kato K, Igarashi K, Kohono S, Takahashi C, Soga T, Tojo A, Gotoh N |
| Citation(s) |
30532069 |
| Submission date |
Jul 05, 2016 |
| Last update date |
Jul 02, 2019 |
| Contact name |
Nishimura Tatsunori |
| E-mail(s) |
tatsunori323@med.nagoya-u.ac.jp
|
| Organization name |
Kanazawa University
|
| Department |
Cancer Reaserch Institute
|
| Lab |
Division of Cancer Cell Biology
|
| Street address |
Kakuma-machi
|
| City |
Kanazawa |
| State/province |
Ishikawa |
| ZIP/Postal code |
920-1192 |
| Country |
Japan |
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| Platforms (1) |
| GPL21185 |
Agilent-072363 SurePrint G3 Human GE v3 8x60K Microarray 039494 [Probe Name Version] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA327801 |
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