School of Medicine, Nankai University, Tianjin 300071, China.
Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University Medical Center, Winston-Salem, NC 27157, USA.
J Mol Cell Biol. 2021 Apr 10;13(1):59-71. doi: 10.1093/jmcb/mjaa050.
Metastases are the main cause of cancer-related mortality in breast cancer. Although significant progress has been made in the field of tumor metastasis, the exact molecular mechanisms involved in tumor metastasis are still unclear. Here, we report that ATOH8-V1, a novel isoform of ATOH8, is highly expressed in breast cancer and is a negative prognostic indicator of survival for patients. Forced expression of ATOH8-V1 dramatically enhances, while silencing of ATOH8-V1 decreases the metastasis of breast cancer cell lines. Moreover, ATOH8-V1 directly binds to the RhoC promoter and stimulates the expression of RhoC, which in turn enhances the metastasis of breast cancer. Altogether, our data demonstrate that ATOH8-V1 is a novel pro-metastatic factor that enhances cancer metastasis, suggesting that ATOH8-V1 is a potential therapeutic target for treatment of metastatic cancers.
转移是乳腺癌相关死亡的主要原因。尽管肿瘤转移领域取得了重大进展，但肿瘤转移的确切分子机制仍不清楚。在这里，我们报告 ATOH8-V1，一种 ATOH8 的新型异构体，在乳腺癌中高度表达，是患者生存的负预后指标。强制表达 ATOH8-V1 显著增强，而沉默 ATOH8-V1 则降低乳腺癌细胞系的转移。此外，ATOH8-V1 直接结合 RhoC 启动子并刺激 RhoC 的表达，从而增强乳腺癌的转移。总之，我们的数据表明 ATOH8-V1 是一种增强癌症转移的新型促转移因子，提示 ATOH8-V1 是治疗转移性癌症的潜在治疗靶点。
