DAB2IP suppresses invadopodia formation through destabilizing ALK by interacting with USP10 in breast cancer

Qingwen Huang; Rui Zhang; Yun Xia; Jie Shen; Hongliang Dong; Xiaolan Li; Deding Tao; Daxing Xie; Liang Liu

doi:10.1016/j.isci.2023.107606

DAB2IP suppresses invadopodia formation through destabilizing ALK by interacting with USP10 in breast cancer

iScience. 2023 Aug 11;26(9):107606. doi: 10.1016/j.isci.2023.107606. eCollection 2023 Sep 15.

Authors

Qingwen Huang^{1

2}, Rui Zhang^{1

2}, Yun Xia³, Jie Shen^{1

2}, Hongliang Dong^{1

2}, Xiaolan Li¹, Deding Tao², Daxing Xie^{1

2}, Liang Liu^{1

2}

Affiliations

¹ Molecular Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China.
² Department of GI Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China.
³ Department of Breast and Thyroid Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China.

Abstract

Invadopodia, being actin-rich membrane protrusions, play a vital role in tumor cell invasion and metastasis. Our previous studies have revealed some functions of the DOC-2/DAB2 interacting protein (DAB2IP) as a tumor suppressor. Nevertheless, the specific role and mechanism of DAB2IP in invadopodia formation remain unclear. Here, we find that DAB2IP effectively suppresses invadopodia formation and metastasis in breast cancer, both in vitro and in vivo. Additionally, DAB2IP could downregulate anaplastic lymphoma kinase (ALK), resulting in the inhibition of tyrosine phosphorylation of Cortactin and the prevention of invadopodia formation. DAB2IP competitively antagonizes the interaction between the deubiquitinating enzyme Ubiquitin-specific peptidase 10 (USP10) and ALK, leading to a decrease in the abundance of ALK protein. In summary, DAB2IP impairs the stability of ALK through USP10-dependent deubiquitination, suppressing Cortactin phosphorylation, thereby inhibiting invadopodia formation and metastasis of breast cancer cells. Furthermore, this study suggests a potential therapeutic strategy for breast cancer treatment.

Keywords: Cancer; Membrane architecture; Molecular interaction; Organizational aspects of cell biology.