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 s...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 AT0H8-V1 is a potential therapeutic target for treatment of metastatic cancers.展开更多
基金This work was supported by the National Science Foundation for Young Scientists of China(81702994)International S&T Cooperation Program of China(2015DFA30420)We thank Dr Ralph A.Reisfeld from the Scripps Research In stitute for his valuable suggestions and for proof-readi ng this manuscript.
文摘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 AT0H8-V1 is a potential therapeutic target for treatment of metastatic cancers.
