Carboxypeptidase A4 regulates stemness and epithelial-mesenchymal transition in triple-negative breast cancer

AbstractTo investigate the significance of carboxypeptidase A4 (CPA4) in triple negative breast cancer (TNBC). The expressions of CPA4, stem and epithelial-mesenchymal transition (EMT) related proteins in TNBC were detected by immunohistochemistry. The relationship between CPA4 and clinicopathological parameters in 168 cases of TNBC was analyzed. The effect of si-CPA4 on MDA-MB-231 was observed. The related proteins were detected by Western Blot. The results indicated the CPA4 positive rate in TNBC was 57.14% (96/168), which was significantly higher than that in non-TNBC tissues (37.5%, 15/40) (χ2 = 5.009,P = 0.025). The positive rate of CPA4 in TNBC tissues was significantly higher than that in breast hyperplasia tissues (20%, 4/20) (χ2 = 9.850,P = 0.002). High CPA4 in patients was positively correlated with NANOG (χ2 = 4.205,P = 0.040) and E-cadherin (χ2 = 11.764,P = 0.040). Vimentin (χ2 = 4.797,P = 0.029), EGFR (χ2 = 4.057,P = 0.044). Si-CPA4 inhibited MDA-MB-231 colony formation, sphere forming, migration and invasion, inhibited the expression of ALDH-1, NANOG and Vimentin, but promoted the expression of E-cadherin. We concluded CPA4 might play an important role in TNBC stemness progression and EMT conversion. CPA4 might be an important therapeutic target for TNBC therapy.