Expression Profiling Identified TRPM7 and HER2 as Potential Targets for the Combined Treatment of Cancer Cells
TRPM7 is a divalent cation-permeable channel that is highly active in cancer cells. The pharmacological inhibitors of TRPM7 have been shown to suppress the proliferation of tumor cells, highlighting TRPM7 as a new anticancer drug target. However, the potential benefit of combining TRPM7 inhibitors w...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-10-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/13/21/1801 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846173557398175744 |
|---|---|
| author | Miyuki Egawa Eva Schmücker Christian Grimm Thomas Gudermann Vladimir Chubanov |
| author_facet | Miyuki Egawa Eva Schmücker Christian Grimm Thomas Gudermann Vladimir Chubanov |
| author_sort | Miyuki Egawa |
| collection | DOAJ |
| description | TRPM7 is a divalent cation-permeable channel that is highly active in cancer cells. The pharmacological inhibitors of TRPM7 have been shown to suppress the proliferation of tumor cells, highlighting TRPM7 as a new anticancer drug target. However, the potential benefit of combining TRPM7 inhibitors with conventional anticancer therapies remains unexplored. Here, we used genome-wide transcriptome profiling of human leukemia HAP1 cells to examine cellular responses caused by the application of NS8593, the potent inhibitor of the TRPM7 channel, in comparison with two independent knockout mutations in the <i>TRPM7</i> gene introduced by the CRISPR/Cas9 approach. This analysis revealed that <i>TRPM7</i> regulates the expression levels of several transcripts, including <i>HER2</i> (<i>ERBB2</i>). Consequently, we examined the <i>TRPM7/HER2</i> axis in several non-hematopoietic cells to show that TRPM7 affects the expression of HER2 protein in a Zn<sup>2+</sup>-dependent fashion. Moreover, we found that co-administration of pharmacological inhibitors of HER2 and TRPM7 elicited a synergistic antiproliferative effect on HER2-overexpressing SKBR3 cells but not on HER2-deficient MDA-MB-231 breast cancer cells. Hence, our study proposes a new combinatorial strategy for treating HER2-positive breast cancer cells. |
| format | Article |
| id | doaj-art-d11788bdb0914527a0cc4af05542b0f6 |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-d11788bdb0914527a0cc4af05542b0f62024-11-08T14:34:33ZengMDPI AGCells2073-44092024-10-011321180110.3390/cells13211801Expression Profiling Identified TRPM7 and HER2 as Potential Targets for the Combined Treatment of Cancer CellsMiyuki Egawa0Eva Schmücker1Christian Grimm2Thomas Gudermann3Vladimir Chubanov4Walther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, 80336 Munich, GermanyWalther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, 80336 Munich, GermanyWalther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, 80336 Munich, GermanyWalther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, 80336 Munich, GermanyWalther-Straub Institute of Pharmacology and Toxicology, Ludwig Maximilian University of Munich, 80336 Munich, GermanyTRPM7 is a divalent cation-permeable channel that is highly active in cancer cells. The pharmacological inhibitors of TRPM7 have been shown to suppress the proliferation of tumor cells, highlighting TRPM7 as a new anticancer drug target. However, the potential benefit of combining TRPM7 inhibitors with conventional anticancer therapies remains unexplored. Here, we used genome-wide transcriptome profiling of human leukemia HAP1 cells to examine cellular responses caused by the application of NS8593, the potent inhibitor of the TRPM7 channel, in comparison with two independent knockout mutations in the <i>TRPM7</i> gene introduced by the CRISPR/Cas9 approach. This analysis revealed that <i>TRPM7</i> regulates the expression levels of several transcripts, including <i>HER2</i> (<i>ERBB2</i>). Consequently, we examined the <i>TRPM7/HER2</i> axis in several non-hematopoietic cells to show that TRPM7 affects the expression of HER2 protein in a Zn<sup>2+</sup>-dependent fashion. Moreover, we found that co-administration of pharmacological inhibitors of HER2 and TRPM7 elicited a synergistic antiproliferative effect on HER2-overexpressing SKBR3 cells but not on HER2-deficient MDA-MB-231 breast cancer cells. Hence, our study proposes a new combinatorial strategy for treating HER2-positive breast cancer cells.https://www.mdpi.com/2073-4409/13/21/1801TRP channelsHER2ERBB2NS8593CP724714zinc |
| spellingShingle | Miyuki Egawa Eva Schmücker Christian Grimm Thomas Gudermann Vladimir Chubanov Expression Profiling Identified TRPM7 and HER2 as Potential Targets for the Combined Treatment of Cancer Cells Cells TRP channels HER2 ERBB2 NS8593 CP724714 zinc |
| title | Expression Profiling Identified TRPM7 and HER2 as Potential Targets for the Combined Treatment of Cancer Cells |
| title_full | Expression Profiling Identified TRPM7 and HER2 as Potential Targets for the Combined Treatment of Cancer Cells |
| title_fullStr | Expression Profiling Identified TRPM7 and HER2 as Potential Targets for the Combined Treatment of Cancer Cells |
| title_full_unstemmed | Expression Profiling Identified TRPM7 and HER2 as Potential Targets for the Combined Treatment of Cancer Cells |
| title_short | Expression Profiling Identified TRPM7 and HER2 as Potential Targets for the Combined Treatment of Cancer Cells |
| title_sort | expression profiling identified trpm7 and her2 as potential targets for the combined treatment of cancer cells |
| topic | TRP channels HER2 ERBB2 NS8593 CP724714 zinc |
| url | https://www.mdpi.com/2073-4409/13/21/1801 |
| work_keys_str_mv | AT miyukiegawa expressionprofilingidentifiedtrpm7andher2aspotentialtargetsforthecombinedtreatmentofcancercells AT evaschmucker expressionprofilingidentifiedtrpm7andher2aspotentialtargetsforthecombinedtreatmentofcancercells AT christiangrimm expressionprofilingidentifiedtrpm7andher2aspotentialtargetsforthecombinedtreatmentofcancercells AT thomasgudermann expressionprofilingidentifiedtrpm7andher2aspotentialtargetsforthecombinedtreatmentofcancercells AT vladimirchubanov expressionprofilingidentifiedtrpm7andher2aspotentialtargetsforthecombinedtreatmentofcancercells |