CAMSAP2 enhances lung cancer cell metastasis by mediating RASAL2 degradation.

AIMS

Cancer metastasis significantly contributes to mortality in lung cancer patients. Calmodulin-regulated spectrin-associated protein family member 2 (CAMSAP2) plays a significant role in cancer cell migration; however, its role in lung cancer metastasis and the underlying mechanism remain largely unknown. The present study aimed to investigate the impact of CAMSAP2 on lung cancer.

MAIN METHODS

The clinical relevance of CAMSAP2 in lung cancer patients was assessed using public database. RNA interference experiments were conducted to investigate role of CAMSAP2 in cell migration through transwell and wound healing assays. Molecular mechanisms were explored by identifying the possible interacting partners and pathways using the BioGRID and KEGG pathway analyses. The impact of CAMSAP2 on Ras protein activator-like 2 (RASAL2)-mediated lung cancer metastasis was investigated through biochemical assays. Additionally, in vivo experimentation using a murine tail vein metastasis model was performed to comprehend CAMSAP2's influence on metastasis.

KEY FINDINGS

A high expression level of CAMSAP2 was associated with poor overall survival in lung cancer patients and it positively correlated with cell migration in non-small cell lung cancer (NSCLC) cell lines. Knockdown of CAMSAP2 inhibited lung cancer cell motility in vitro and metastasis in vivo. Proteomic and biochemical analyses revealed the interaction between CAMSAP2 and RASAL2, which facilitates the degradation of RASAL2 through the ubiquitin-proteasome system. These degradation processes resulted in the activation of the extracellular signal-regulated kinase (ERK) signaling pathway, thereby promoting lung cancer metastasis. Collectively, the results of this study suggest that CAMSAP2 is a crucial regulator of cancer cell migration and metastasis and a promising therapeutic target for lung cancer.