SMARCAD1 knockdown uncovers its role in breast cancer cell migration, invasion, and metastasis

ABSTRACT

Objective: Breast cancer is the most common cancer seen in women worldwide and breast cancer patients are at high risk of recurrence in the form of metastatic disease. Identification of genes associated with invasion and metastasis is crucial in order to develop novel anti-metastasis targeted therapy. It has been demonstrated that the DEAD-BOX helicase DP103 was implicated in breast cancer invasion and metastasis. SMARCAD1 is also a DEAD/H box-containing helicase, suggested to play a role in genetic instability. However, its involvement in cancer migration, invasion, and metastasis has never been explored.

Research design and methods: Using two different designs of shRNA targeting SMARCAD1, we investigated the impact of SMARCAD1 knockdown on the migration, invasion, and metastasis potential of the breast cancer cells MDA-MB-231 and T47D.

Results: We observed that SMARCAD1 knockdown in the invasive breast cancer cells MDA-MB-231, unlike in the non-invasive breast cancer cells T47D, was associated with an increased cell-cell adhesion and a significant decrease in cell migration, invasion, and metastasis due at least in part to a strong inhibition of STAT3 phosphorylation.

Conclusions: These results indicate that SMARCAD1 is involved in breast cancer metastasis and can be a promising target for metastatic breast cancer therapy.

KEYWORDS:

• Breast cancer
• invasion
• metastasis
• migration
• STAT3
• SMARCAD1

Acknowledgments

Thanks to Jean Viallet of Inovotion for doing the first part of the chick embryo metastasis assay. Thanks to Dr. Mahmood Al Sultan for technical help. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Declaration of interest

This work was supported by a College of Medicine & Health Sciences grant (NP-10-11/107) and the United Arab Emirates University Program for Advanced Research grant (3IMI84). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.