DNALK2 inhibits the proliferation and invasiveness of breast cancer MDA-MB-231 cells through the Smad-dependent pathway.

Breast cancer is one of the most common malignant neoplasms diagnosed in females worldwide. Bone morphogenetic proteins (BMPs), which belong to the TGF-β superfamily, regulate a wide range of cellular responses including cell proliferation, differentiation, adhesion, migration and apoptosis in breast cancer. BMPs can bind to type I and II serine/threonine kinase receptors to regulate cell proliferation, invasion, migration, and apoptosis. Type I receptors are expressed in various breast cancer cell lines and primary tumor samples. Activin‑like kinase 2 (ALK2) is generally expressed in breast cancer cells (MDA-MB-231, MCF7, SK-BR-3 and MDA-MB‑468); however, the effect of ALK2 on the proliferation and metastasis of breast cancer cells remains unknown. We used a dominant-negative mutant of ALK2 to research the function of ALK2. We aimed to ascertain whether dominant-negative mutant ALK2 adenovirus vector (DNALK2) receptors can compete with wild-type ALK2 receptors. The present study showed that DNALK2 inhibited the growth, migration and metastasis of breast cancer cells by inhibiting the SMAD-dependent pathway and downregulating connective tissue growth factor and inhibitor of differentiation 1 expression, in vivo and in vitro. These observations indicate that ALK2 is a potential therapeutic agent for the treatment of breast cancer.