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| Status |
Public on Mar 20, 2024 |
| Title |
FGFR inhibition blocks NF-ĸB-dependent glucose metabolism and confers metabolic vulnerabilities in cholangiocarcinoma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Genomic alterations that activate FGFR2 are common in intrahepatic cholangiocarcinoma (ICC) and confer sensitivity to treatment with FGFR inhibitors. However, the depth and duration of responses are often limited. Elucidating the FGFR2-driven oncogenic program and the adaptions to FGFR inhibition is needed to gain insight into the biology of these tumors and inform future therapeutic development. Here, we conducted transcriptomic analysis of patient-derived models to define the pathways that fuel tumor growth downstream of oncogenic FGFR2 signaling in ICC and to uncover compensatory mechanisms associated with pathway inhibition. For these studies, we performed RNA sequencing in our FGFR-driven ICC models, including cell line ICC13-7 , PDX MG69 and MG212. We treated ICC13-7 with DMSO or 75 nM Futibatinib for 4/12/24 hours, MG69 with vehicle or Futibatinib for 14 days and MG212 with vehicle or Pemigatinib for 11 days followed by RNA sequencing. In addition, ICC13-7 cells were transfected with siScramble and siRELA and followed by RNA sequencing.
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| Overall design |
To identify the oncogenic program controlled by FGFR signaling in FGFR2-fusion+ ICC, we took advantage of a series of patient derived FGFR2-fusion+ ICC models, including cell lines and PDX. We then treated the models with FGFR inhibitor or control to perform the RNA sequencing and analyzed the gene expression profiling.
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| Contributor(s) |
Zhen Y |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Aug 25, 2023 |
| Last update date |
Apr 29, 2024 |
| Contact name |
Yuanli Zhen |
| Organization name |
mgh
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| Department |
cancer center
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| Street address |
185 cambridge street
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| City |
boston |
| ZIP/Postal code |
02114 |
| Country |
USA |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (30)
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| GSM7734633 |
ICC13-7 cells, 75 nm Futibatinib, 4 hours, replicate 1 |
| GSM7734634 |
ICC13-7 cells, 75 nm Futibatinib, 4 hours, replicate 2 |
| GSM7734635 |
ICC13-7 cells, 75 nm Futibatinib, 4 hours, replicate 3 |
| GSM7734636 |
ICC13-7 cells, 75 nm Futibatinib, 12 hours, replicate 1 |
| GSM7734637 |
ICC13-7 cells, 75 nm Futibatinib, 12 hours, replicate 2 |
| GSM7734638 |
ICC13-7 cells, 75 nm Futibatinib, 12 hours, replicate 3 |
| GSM7734639 |
ICC13-7 cells, 75 nm Futibatinib, 24 hours, replicate 1 |
| GSM7734640 |
ICC13-7 cells, 75 nm Futibatinib, 24 hours, replicate 2 |
| GSM7734641 |
ICC13-7 cells, 75 nm Futibatinib, 24 hours, replicate 3 |
| GSM7734642 |
PDX MG212, vehicle, replicate 1 |
| GSM7734643 |
PDX MG212, vehicle, replicate 2 |
| GSM7734644 |
PDX MG212, vehicle, replicate 3 |
| GSM7734645 |
PDX MG212, 1 mg/kg pemigatinib, replicate 1 |
| GSM7734646 |
PDX MG212, 1 mg/kg pemigatinib, replicate 2 |
| GSM7734647 |
PDX MG212, 1 mg/kg pemigatinib, replicate 3 |
| GSM7734648 |
PDX MG69, vehicle, replicate1 |
| GSM7734649 |
PDX MG69, vehicle, replicate2 |
| GSM7734650 |
PDX MG69, vehicle, replicate3 |
| GSM7734651 |
PDX MG69, 50 mg/kg Futibatinib, replicate1 |
| GSM7734652 |
PDX MG69, 50 mg/kg Futibatinib, replicate2 |
| GSM7734653 |
PDX MG69, 50 mg/kg Futibatinib, replicate3 |
| GSM8239030 |
FGFR2-fusion+ intrahepatic cholangiocarcinoma, siscramble, replicate1 |
| GSM8239031 |
FGFR2-fusion+ intrahepatic cholangiocarcinoma, siscramble, replicate2 |
| GSM8239032 |
FGFR2-fusion+ intrahepatic cholangiocarcinoma, siscramble, replicate3 |
| GSM8239033 |
FGFR2-fusion+ intrahepatic cholangiocarcinoma, siRELA, replicate1 |
| GSM8239034 |
FGFR2-fusion+ intrahepatic cholangiocarcinoma, siRELA, replicate2 |
| GSM8239035 |
FGFR2-fusion+ intrahepatic cholangiocarcinoma, siRELA, replicate3 |
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| Relations |
| BioProject |
PRJNA1009431 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE241735_YZb2_allSamples_raw.txt.gz |
282.6 Kb |
(ftp)(http) |
TXT |
| GSE241735_processed_file_TPM_values_GSM8239030-GSM8239035.xlsx |
2.8 Mb |
(ftp)(http) |
XLSX |
| GSE241735_raw_counts_MG212.txt.gz |
506.9 Kb |
(ftp)(http) |
TXT |
| GSE241735_rawcnt_allSamples_icc13-7.tsv.txt.gz |
483.4 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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