Chromodomain Helicase/ATPase DNA-Binding Protein 1-like Gene(CHD1L) Expression And Implications For Invasion And Metastasis Of Breast Cancer

Background and aim: Chromodomain helicase/ATPase DNA-binding protein 1-like gene(CHD1L), also known as ALC1(amplified in liver cancer 1 gene), is a new oncogene amplified in many solid tumors. Whether this gene plays a role in invasion and metastasis of breast cancer is unknown.Methods: Immunohistochemistry was performed to detect the expression of CHD1 L in patients with invasive ductal carcinoma and normal mammary glands. Chemotaxis, wound healing, and Transwell invasion assays were also performed to examine cell migration and invasion. Western blot analysis was conducted to detect the expression of CHD1 L, MMP-2, MMP-9, p-Akt/Akt, p-ARK5/ARK5, and pm TOR/m TOR. Moreover, ELISA was carried out to detect the expression levels of MMP-2 and MMP-9. Nude mice xenograft model was used to detect the invasion and metastasis of breast cancer cell lines.Results: CHD1 L overexpression was observed in 112 of 268 patients(41.8%). This overexpression was associated with lymph node metastasis(P = 0.008), tumor differentiation(P = 0.020), distant metastasis(P = 0.026), MMP-2(P = 0.035), and MMP-9 expression(P = 0.022). In the cell experiment, reduction of CHD1 L inhibited the invasion and metastasis of breast cancer cells by mediating MMP-2 and MMP-9 expression. CHD1 L knockdown via si RNA suppressed EGF-induced p-Akt, p-ARK5, and pm TOR. This knockdown inhibited the metastasis of breast cancer cells into the lungs of SCID mice.Conclusion: CHD1 L promoted the invasion and metastasis of breast cancer cells via the PI3K/Akt/ ARK5/m TOR/MMP signaling pathway. This study identified CHD1 L as a potential anti-metastasis target for therapeutic intervention in breast cancer.