乳腺癌的转移通常导致大多数临床患者死亡。因此，在乳腺癌的早期阶段诊断转移对于改善预后至关重要。我们观察到，Dicer蛋白在高侵袭性乳腺癌细胞中明显降低，通常与不良临床结果相关。因此，我们的目标是阐明Dicer在乳腺癌中的分子调节机制，以提供一种新的治疗靶点。在本研究中，我们发现Dicer表达与转移和侵袭相关，但不影响乳腺癌细胞的稳定性。重要的是，我们确定了Dicer蛋白降解的调节机制，即伴随体介导的自噬（CMA）介导的降解，这是减少Dicer蛋白表达并导致癌症转移的主要机制。我们发现，热休克同源物71-kDa蛋白（Hsc70），作为CMA相关因子，与Dicer上的CMA靶向基序I333A/K334A交互，通过CMA促进降解。总之，我们的发现提示Dicer与癌症转移高度相关，揭示了CMA介导Dicer降解在乳腺癌中的促进肿瘤作用。©2023 Wiley Periodicals LLC。

Metastasis in breast cancer usually lead to the majority of deaths on clinical patients. Accordingly, diagnosis of metastasis at the early stage in breast cancer is important to improve the prognosis. We observed that Dicer protein levels are significant decrease in highly invasive breast cancer cells and usually correlated with poor clinical outcomes. Following, we aim to clarify the molecular regulatory mechanism of this phenomenon in breast cancer to provide a new therapeutic target. In this study, we obtained that Dicer expression correlated with metastasis and invasion without affect cell stability in breast cancer cells. Importantly, we identified the regulatory mechanism of Dicer protein degradation, the chaperone-mediated autophagy (CMA)-mediated degradation that is major mechanism to decrease Dicer protein expression and lead to cancer metastasis. We discovered that heat shock cognate 71-kDa protein (Hsc70) which as a CMA-related factor interacts with the CMA-targeting motif I333A/K334A on Dicer to promote degradation through CMA. Taken together, our findings hint that Dicer highly correlated with cancer metastasis, we reveal the tumor-promoting effect of CMA-mediated Dicer degradation in breast cancer.© 2023 Wiley Periodicals LLC.