ARMCX2 (ALEX2) is an X-chromosome-encoded armadillo repeat protein originally identified by cDNA cloning, with transcripts broadly expressed across human tissues and reduced or lost in several epithelial carcinomas including lung, prostate, colon, pancreas, and ovarian tumors PMID:11162520. In cisplatin-resistant ovarian cancer cells, the ARMCX2 promoter acquires CpG hypermethylation that transcriptionally silences the gene; treatment with the demethylating agent 2-deoxy-5'-azacytidine restores ARMCX2 expression and resensitizes cells to cisplatin, linking epigenetic silencing of ARMCX2 to acquired chemoresistance PMID:22249249. As a member of the GPRASP/ARMCX subfamily, ARMCX2 carries a mitochondrial targeting transmembrane domain and, in complex with TRAK2 and MIRO, participates in axonal mitochondrial trafficking and regulation of mitochondrial size and division PMID:33267763. Beyond these observations, direct mechanistic characterization of ARMCX2's molecular activity has not been established in the available corpus.
| Year | Confidence | Finding | PMIDs | Journal |
|---|---|---|---|---|
| 2001 | Low | ARMCX2 (ALEX2) encodes a novel human armadillo repeat protein whose gene co-localizes with ALEX1 and ALEX3 to chromosome Xq21.33-q22.2. ALEX2 transcripts are expressed in all human tissues examined except peripheral blood leukocytes, and expression is lost or significantly reduced in lung, prostate, colon, pancreas, and ovarian carcinomas, suggesting a role in suppression of epithelial tumors. | PMID:11162520 | Biochemical and biophysical research communications |
| 2012 | Medium | ARMCX2 promoter CpG sites acquire hypermethylation in cisplatin-resistant ovarian cancer cells (A2780/cp70) compared with parental sensitive cells, and this hypermethylation is associated with transcriptional silencing of ARMCX2. Re-expression is induced by the demethylating agent 2-deoxy-5'-azacytidine alongside resensitization to cisplatin. ARMCX2 methylation was also detected in drug-resistant ovarian cancer-sustaining (side population) cells and in tumors at relapse, implicating DNA methylation-driven silencing as a mechanism contributing to chemoresistance. | PMID:22249249 | Oncogene |
| 2021 | Low | ARMCX2, as a member of the GPRASP/ARMCX subfamily 2, possesses a mitochondrial targeting transmembrane domain and, in complex with TRAK2 and MIRO, is involved in trafficking of mitochondria in axons and in the regulation of mitochondrial size and division, influencing the cell cycle. | PMID:33267763 | Current topics in medicinal chemistry |