KRT15通过Wnt/β-catenin信号通路促进乳腺癌细胞增殖与侵袭并抑制铁死亡

KRT15 Regulates Wnt/β-catenin Signaling Pathway to Inhibit Invasion and Ferroptosis of Breast Cancer Cells

乳腺癌是女性最常见的癌症类型。既往研究表明,角蛋白15(Keratin 15,KRT15)参与调控多种恶性肿瘤的发生发展。然而,目前KRT15在乳腺癌中的调控机制尚不清楚。本研究中,我们发现在乳腺癌细胞过表达KRT15可促进其增殖、侵袭和上皮-间质转化,并抑制凋亡,而敲减KRT15则表现出相反的表型。此外,通过Western blot和铁比色检测发现KRT15抑制乳腺癌细胞铁死亡,KRT15过表达的乳腺癌细胞Wnt/β-catenin通路相关蛋白表达量增加。因此,KRT15可能通过增强Wnt/β-catenin通路抑制铁死亡在乳腺癌发展中发挥作用,提示KRT15是乳腺癌的潜在驱动基因。

Breast cancer is one of the most common cancers in woman.Previous studies have shown that keratin 15(KRT15)is involved in the regulation of the occurrence and development of many kinds of malignant tumors.However,the role and molecular mechanism of KRT15 in breast cancer remains unclear.In this study,we found overexpression KRT15 can promote the proliferation,invasion,and epithelial-mesenchymal transformation.As a results KRT15 overexpression reduces apoptosis of breast cancer cells.While KRT15 knockdown showed the opposite phenotype.In addition,KRT15 inhibited ferroptosis of breast cancer cells analyzed by Western blot and iron colorimetric test kit.The Wnt/β-catenin pathway related proteins expression increased in breast cancer cells with overexpression of KRT15.According to our research results,KRT15 plays an important role in the progression of breast cancer by enhancement of Wnt/β-catenin pathway functions and inhibition of ferroptosis which indicates that KRT15 is a potential driving gene for breast cancer.