Murugan Nirosha J, Genautis Emma, Voutsadakis Ioannis A
Department of Biology, Wilfrid Laurier University, Waterloo, ON N2L 6C2, Canada.
Allen Discovery Center, Tufts University, Medford, MA 02155, USA.
Int J Mol Sci. 2025 Apr 11;26(8):3639. doi: 10.3390/ijms26083639.
Calcium movement and concentration in the cell plays significant roles in normal physiology and in diseases such as cancer. The significance of this ion in oncogenesis suggests that membrane-relevant proteins are involved in its regulation and are deregulated in various cancers. These channels and transporters could be targets for therapeutic interventions. An evaluation of the expression of transient receptor potential (TRP) channels in prostate cancer was performed using publicly available genomic and proteome data. Two TRP family members with high expression in prostate cancers, TRPML2 and TRPM4, were chosen for further analysis the uncover the associations of their level of expression with clinical and pathologic prostate cancer characteristics. Several TRP channels were expressed in prostate cancers at the protein level including TRPM4, TRPML1, TRPML2, TRPC1 and TRPP3. At the mRNA level, MCOLN2 and TRPM4 were strongly expressed in a sub-set of prostate cancers. Cases with high MCOLN2 mRNA expression were associated with frequent ERG fusions and a trend for better survival outcomes. In contrast, prostate cancer cases with high TRPM4 mRNA expression were associated with lower ERG fusion frequency than cases with low TRPM4 mRNA expression. The prognosis of prostate cancers with high TRPM4 expression was not different from the prognosis with counterparts having low TRPM4 mRNA expression. TRP channels were expressed in sub-sets of prostate cancers. The two well-expressed channels of the super family, TRPML2 and TRPM4, have divergent associations with the most prevalent prostate cancer molecular aberrations, ERG fusions. These results imply diverse regulations of the TRP channels that would have to be taken into consideration when devising therapeutic interventions targeting individual channels.
细胞内钙的移动和浓度在正常生理过程以及癌症等疾病中发挥着重要作用。这种离子在肿瘤发生中的重要性表明，与膜相关的蛋白质参与其调节，且在各种癌症中失调。这些通道和转运蛋白可能是治疗干预的靶点。利用公开可用的基因组和蛋白质组数据对前列腺癌中瞬时受体电位（TRP）通道的表达进行了评估。选择在前列腺癌中高表达的两个TRP家族成员TRPML2和TRPM4进行进一步分析，以揭示它们的表达水平与临床和病理前列腺癌特征之间的关联。几种TRP通道在前列腺癌中呈蛋白质水平表达，包括TRPM4、TRPML1、TRPML2、TRPC1和TRPP3。在mRNA水平上，MCOLN2和TRPM4在一部分前列腺癌中强烈表达。MCOLN2 mRNA高表达的病例与频繁的ERG融合以及更好的生存结果趋势相关。相比之下，TRPM4 mRNA高表达的前列腺癌病例与TRPM4 mRNA低表达的病例相比，ERG融合频率较低。TRPM4高表达的前列腺癌的预后与TRPM4 mRNA低表达的对应病例的预后没有差异。TRP通道在一部分前列腺癌中表达。超家族中两个表达良好的通道TRPML2和TRPM4与最常见的前列腺癌分子畸变ERG融合有不同的关联。这些结果意味着在设计针对单个通道的治疗干预措施时，必须考虑TRP通道的不同调节。
