Smad1 promotes colorectal cancer cell migration through Ajuba transactivation

Oncotarget
Daming YangHao Jia

Abstract

SMAD family member 1 (Smad1) have been involved in metastatic progression of many cancer types. However, the detailed molecular signalling pathway underlying the regulatory link between Smad1 and metastasis remains elusive. Here, we demonstrate that Smad1 promotes migration of colorectal cancer (CRC) cells by inducing Snail and Ajuba expression simultaneously, but no apparent effect on Twist1 expression. Remarkably, E-cadherin, the best known Snail/Ajuba target gene is downregulated by Smad1 expression. Further, depletion of Ajuba in HCT116 cells significantly dampens the cell migration capability induced by Smad1 overexpression, suggesting that Ajuba is required for Smad1 to induce cell migration. Moreover, clinical analysis shows a significant positive correlation between the level of Smad1 and Ajuba in CRC samples. Together, our data provides the first evidence of the regulatory network of Smad1/Snail/Ajuba axis in CRC migration, suggesting that Smad1 and Ajuba are potential new therapeutic targets and prognostic factors for CRC.

References

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Citations

Jul 19, 2020·Cancers·Noëlle DommannDeborah Stroka
Sep 15, 2020·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Priyanka Florina KarmokarMohammad Safiqul Islam
Mar 19, 2019·Oncology Letters·Weiyun WuJuanhua Quan
Dec 30, 2020·Experimental Dermatology·Krista Schleicher, Daniel Schramek
Dec 19, 2020·Open Medicine·Changming LiuHuihong Chen
May 6, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Tianshi ChenHao Jia

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Methods Mentioned

BETA
PCR
transfection

Software Mentioned

SPSS

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