Dataset Information

Chromodomain Helicase/ATPase DNA-Binding Protein 1-Like Gene (CHD1L) Expression and Implications for Invasion and Metastasis of Breast Cancer.

ABSTRACT:

Background

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 CHD1L 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 CHD1L, MMP-2, MMP-9, pAkt/Akt, pARK5/ARK5, and pmTOR/mTOR. 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

CHD1L 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 CHD1L inhibited the invasion and metastasis of breast cancer cells by mediating MMP-2 and MMP-9 expression. CHD1L knockdown via siRNA suppressed EGF-induced pAkt, pARK5, and pmTOR. This knockdown inhibited the metastasis of breast cancer cells into the lungs of SCID mice.

Conclusions

CHD1L promoted the invasion and metastasis of breast cancer cells via the PI3K/Akt/ARK5/mTOR/MMP signaling pathway. This study identified CHD1L as a potential anti-metastasis target for therapeutic intervention in breast cancer.

SUBMITTER: Mu QJ

PROVIDER: S-EPMC4657932 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Cholangiocarcinoma is a highly malignant form of gastrointestinal cancer with an unfavorable prognosis. The novel oncogene chromodomain helicase/ATPase DNA binding protein 1-like (CHD1L) has been confirmed to serve a vital role in numerous types of cancer, including liver cancer. Mismatch repair (MMR) is a common DNA repair process that contributes to the preservation of the integrity and stability of genetic substances. Human mutL homolog 1 gene (hMLH1) is an important MMR protein family member. The present study aimed to evaluate the pathological and clinical features of cholangiocarcinoma, and to investigate the clinical significance of CHD1L and hMLH1 expression in cholangiocarcinoma. A total of 108 samples from cholangiocarcinoma tumor tissues and 60 samples from normal bile duct tissue were obtained from patients admitted to The Second Affiliated Hospital of Nanchang University between May 2005 and May 2014. All cholangiocarcinoma cases were pathologically confirmed. The expression of CHD1L and hMLH1 was examined by immunohistochemistry analysis. The expression of CHD1L in cholangiocarcinoma (94.44%) was significantly higher than in normal bile duct tissues (40.00%). CHD1L expression was associated with gallstone history, serum carbohydrate antigen 19-9 (CA19-9) level and Tumor-Node-Metastasis (TNM) stage (P<0.05). hMLH1 expression in cholangiocarcinoma (77.78%) was significantly lower than in normal bile duct tissues (96.67%), and was associated with gender, age, serum CA19-9 level, the presence of hepatitis B virus surface antigen, TNM stage and tumor diameter (P<0.05). Kaplan-Meier survival curve analysis indicated that the 3-year accumulative survival rates for CHD1L-positive and -negative patients differed significantly (P<0.05; 17.90 and 83.33%, respectively). There was no statistically significant difference (P>0.05) between the 3-year accumulate survival rates for hMLH1-positive and -negative patients (38.90 and 33.30%, respectively). High CHD1L expression and low hMLH1 expression levels were observed in patients with cholangiocarcinoma, and their abnormal expression patterns were associated with the progression of malignancy and an unfavorable disease prognosis. Therefore, CHD1L and hMLH1 may be potential prognostic biomarkers for cholangiocarcinoma.