Department of Breast Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, China.
Biomed Res Int. 2020 Nov 10;2020:1703531. doi: 10.1155/2020/1703531. eCollection 2020.
Arachidonate lipoxygenases (ALOX) have been implicated in playing a critical role in tumorigenesis, development, and metastasis. We previously reported that ALOX12 is involved in breast cancer chemoresistance. In this study, we demonstrate that the ALOX5 activation correlates with the HER2 expression and mediates breast cancer growth and migration. We found that the ALOX5 expression and activity were upregulated in breast cancer patients, particularly in those tissues with HER2-positive. ALOX5 upregulation was also observed in HER2-positive breast cancer cells. In contrast, HER2 inhibition led to decreased expression and activity of ALOX5 but not ALOX5AP, suggesting that HER2 specifically regulates the ALOX5 expression and activity in breast cancer cells. We further demonstrated that ALOX5 is important for breast cancer biological activities with the predominant roles in growth and migration, likely through RhoA, focal adhesion, and PI3K/Akt/mTOR signaling but not epithelial mesenchymal transition (EMT). Our work is the first to report a correlation between the ALOX5 activity and HER2 overexpression in breast cancer. Our findings also highlight the therapeutic value of inhibiting ALOX5 in breast cancer, particularly those patients with the HER2 overexpression.
花生四烯酸脂加氧酶（ALOX）在肿瘤发生、发展和转移中起着关键作用。我们之前的研究报告称，ALOX12 参与了乳腺癌的化疗耐药性。在这项研究中，我们证明了 ALOX5 的激活与 HER2 的表达相关，并介导了乳腺癌的生长和迁移。我们发现，在乳腺癌患者中，尤其是在 HER2 阳性的组织中，ALOX5 的表达和活性上调。在 HER2 阳性的乳腺癌细胞中也观察到 ALOX5 的上调。相比之下，HER2 的抑制导致 ALOX5 的表达和活性降低，但 ALOX5AP 不受影响，这表明 HER2 特异性调节乳腺癌细胞中 ALOX5 的表达和活性。我们进一步证明，ALOX5 对于乳腺癌的生物学活性很重要，其在生长和迁移方面的作用更为突出，可能是通过 RhoA、焦点黏附以及 PI3K/Akt/mTOR 信号通路，但不是上皮间质转化（EMT）。我们的工作首次报道了 ALOX5 活性与乳腺癌中 HER2 过表达之间的相关性。我们的研究结果还突出了抑制 ALOX5 在乳腺癌中的治疗价值，尤其是在那些 HER2 过表达的患者中。
