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| Status |
Public on Mar 16, 2023 |
| Title |
LIMK2 promotes melanoma tumor growth and metastasis through G3BP1-ESM1 pathway-mediated apoptosis inhibition |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Melanoma is the leading cause of skin cancer-related deaths, and current melanoma therapies, including targeted therapies and immunotherapies, benefit only a subset of metastatic melanoma patients due to either intrinsic or acquired resistance. LIM domain kinase 2 (LIMK2) is a serine/threonine kinase that plays an important role in the regulation of actin filament dynamics. Here, we show that LIMK2 is overexpressed in melanoma, and its genetic or pharmacological inhibition impairs melanoma tumor growth and metastasis in both cell culture and mice. To determine the mechanism by which LIMK2 promotes melanoma tumor growth and metastatic progression, we performed a phosphoproteomics analysis and identified G3BP1 as a key LIMK2 target, which mirrored the effects of LIMK2 inhibition when inhibited. To further determine the role of G3BP1 downstream of LIMK2, we knocked down the expression of G3BP1, performed RNA-seq analysis, and identified ESM1 as a downstream target of G3BP1. G3BP1 was required for ESM1 mRNA stability, and ESM1 ectopic expression rescued LIMK2 or G3BP1 inhibition-induced suppression of melanoma growth and metastatic attributes. These results collectively identify the LIMK2→G3BP1→ESM1 pathway as a facilitator of melanoma tumor growth and metastasis and document that LIMK2 is a therapeutically tractable target for melanoma therapy.
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| Overall design |
Total RNA was extracted from all cells, followed by poly-A selection and RNA-sequencing using Illumina Hi-Seq 2500 platform, with three biological replicates for each transformed sample.
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| Contributor(s) |
Kumar R, Wajapeyee N |
| Citation missing |
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| Submission date |
Dec 08, 2021 |
| Last update date |
Mar 16, 2023 |
| Contact name |
Narendra Wajapeyee |
| E-mail(s) |
nwajapey@uab.edu
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| Phone |
205-934-5331
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| Organization name |
University of Alabama at Birmingham
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| Department |
Department of Biochemistry and Molecular Genetics
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| Street address |
720 20th Street South, Kaul 540A
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| City |
Birmingham |
| State/province |
AL |
| ZIP/Postal code |
35233 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA787262 |
| SRA |
SRP349843 |
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