[Retracted] Role of camsap3 on lung cancer cell invasion and angiogenesis under hypoxic condition

Suthasinee Seephan, Faculty of Pharmaceutical Sciences

Abstract

Cancer metastasis is the leading cause of death among cancer patients. The identification of molecular mechanisms that play a role in cancer metastasis is of interest. Numerous microtubule-associated proteins significantly contribute to the aggressive behaviors of cancer. Even though calmodulin-regulated spectrin-associated protein 3 (CAMSAP3), a minus-end microtubule-binding protein, was found to be associated with lung cancer motility, its function on the metastasis of lung cancer is still largely unexplored. This study demonstrated that CAMSAP3-deficient lung cancer cells had high invasive ability and stimulated angiogenic activities including endothelial cell proliferation and tube formation, which was extensively decreased by the introduction of exogenous CAMSAP3 wild-type. Hypoxia-inducible factor-1 (hif-1α) mRNA was highly expressed in the absence of CAMSAP3, leading to an increase in its downstream target mRNA expressions, including vascular endothelial growth factor (vegf) and matrix metalloproteinases (mmp2 and mmp9). After performing a proteomic analysis, nucleolin was shown to bind to CAMSAP3, which resulted in the dissociation of nucleolin from hif-1α mRNA. In contrast, in the absence of CAMSAP3, nucleolin interacted with and stabilized hif-1α mRNA, indicating that nucleolin was necessary for CAMSAP3 regulating hif-1α mRNA stability. Furthermore, CAMSAP3 knockout was able to mediate in vivo lung metastasis and angiogenesis. Therefore, CAMSAP3 was considered as a promising therapeutic target for inhibiting lung cancer metastasis.