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| Status |
Public on Mar 04, 2019 |
| Title |
MicroRNA-mediated suppression of the TGF-ß pathway confers transmissible and reversible CDK4/6 inhibitor resistance (miRNA array) |
| Platform organisms |
Homo sapiens; Human alphaherpesvirus 1; Human alphaherpesvirus 2; Cytomegalovirus; Lymphocryptovirus; Rhadinovirus; JC polyomavirus; Human immunodeficiency virus 1; Merkel cell polyomavirus; Betapolyomavirus hominis; Betapolyomavirus macacae |
| Sample organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by array
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| Summary |
CDK4/6 inhibition is now part of the standard armamentarium for patients with estrogen receptor (ER)-positive breast cancer, so that defining mechanisms of resistance is a pressing issue. Here, we identify increased CDK6 expression as a key determinant of acquired resistance after exposure to palbociclib in ER-positive breast cancer cells. Increased CDK6 in resistant cells was dependent on TGF-β pathway suppression via miR-432-5p expression. Exosomal miR-432-5p expression mediated transfer of the resistance phenotype between neighboring cell populations. We confirmed these data in pre-treatment and post-progression biopsies from a parotid cancer patient who had responded to ribociclib, demonstrating clinical relevance of this mechanism. Additionally, the CDK4/6 inhibitor resistance phenotype can be reversed in vitro and in vivo by a prolonged drug holiday.
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| Overall design |
T47D cells were cultured to palbociclib resistance. We extracted RNA from parental, resistant, and parental T47D cells cultured in resistant cell media and analysed the expression of 3100 miRNAs using the Exiqon 7th generation miRCURY LNATM microRNA
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| Contributor(s) |
Cornell L, Shapiro GI |
| Citation(s) |
30840889 |
| |
| Submission date |
Jul 26, 2018 |
| Last update date |
Apr 17, 2019 |
| Contact name |
Liam Cornell |
| E-mail(s) |
liam_cornell@dfci.harvard.edu
|
| Organization name |
Dana-Farber Cancer Institute
|
| Street address |
450 brookline avenue
|
| City |
boston |
| State/province |
MASSACHUSETTS |
| ZIP/Postal code |
02215 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL19128 |
Exiqon miRCURY LNA microRNA array; 7th generation - hsa, mmu & rno (miRBase 18.0) |
|
| Samples (9)
|
| GSM3308142 |
pabociclib resistant cell RNA repeat 1 |
| GSM3308143 |
pabociclib resistant cell RNA repeat 2 |
| GSM3308144 |
pabociclib resistant cell RNA repeat 3 |
| GSM3308145 |
RNA from parental cells gown in resistant cell media repeat 1 |
| GSM3308146 |
RNA from parental cells gown in resistant cell media repeat 2 |
| GSM3308147 |
RNA from parental cells gown in resistant cell media repeat 3 |
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| This SubSeries is part of SuperSeries: |
| GSE117748 |
MicroRNA-mediated suppression of the TGF-β pathway confers transmissible and reversible CDK4/6 inhibitor resistance |
|
| Relations |
| BioProject |
PRJNA483059 |
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