The positive feedback loop between epithelial-mesenchymal transition (EMT) and M2-like tumor-associated macrophages (TAM-M2) contributes to tumor growth and metastasis. This research aims to investigate the regulatory mechanism of CCDC34 in the maintenance of this loop in lung squamous cell carcinoma (LUSC). Lentiviral vectors were used to knock down CCDC34, and the impact of CCDC34 knockdown on metastasis-like behaviors of LUSC cells was analyzed. LUSC cell-conditioned medium was used to analyze the influence of CCDC34 knockdown in LUSC on the M2 polarization of TAM and to verify the positive feedback loop of EMT and TAM-M2 polarization. CCDC34 was upregulated in LUSC and was related to poor patient prognosis. Knockdown of CCDC34 inhibited EMT in LUSC, decreased M2 polarization of TAM, impaired the positive feedback loop between EMT and TAM-M2 polarization, and suppressed metastasis of mouse LLC cells. TCF12 bound to the CCDC34 promoter to induce its transcription. Overexpression of CCDC34 overturned the blockade of EMT and TAM-M2 polarization by knockdown of TCF12 and promoted metastasis. Consequently, this study elucidates the essential roles of CCDC34 in the positive feedback loop between EMT and TAM-M2 in LUSC, thereby substantiating its potential as a prognostic marker.
Yu et al. (Fri,) studied this question.