Malla RamaRao, Kundrapu Durga Bhavani, Bhamidipati Priyamvada, Nagaraju Ganji Purnachandra, Muniraj Nethaji
Cancer Biology Laboratory, Department of Biochemistry and Bioinformatics, GITAM School of Science, GITAM (Deemed to be University), Visakhapatnam 530045, Andhra Pradesh, India.
Department of Hematology and Oncology, Heersink School of Medicine, University of Alabama, Birmingham, AL 35233, USA.
Cancers (Basel). 2023 Dec 6;15(24):5728. doi: 10.3390/cancers15245728.
The YAP protein is a critical oncogenic mediator within the Hippo signaling pathway and has been implicated in various cancer types. In breast cancer, it frequently becomes activated, thereby contributing to developing drug-resistance mechanisms. Recent studies have underscored the intricate interplay between YAP and ferroptosis within the breast tumor microenvironment. YAP exerts a negative regulatory effect on ferroptosis, promoting cancer cell survival and drug resistance. This review offers a concise summary of the current understanding surrounding the interplay between the YAP pathway, ferroptosis, and drug-resistance mechanisms in both bulk tumor cells and cancer stem cells. We also explore the potential of natural compounds alone or in combination with anticancer therapies for targeting the YAP pathway in treating drug-resistant breast cancer. This approach holds the promise of enhancing the effectiveness of current treatments and paving the way for developing novel therapeutics.
YAP蛋白是Hippo信号通路中的一种关键致癌介质,与多种癌症类型有关。在乳腺癌中,它经常被激活,从而导致耐药机制的形成。最近的研究强调了YAP与乳腺癌肿瘤微环境中的铁死亡之间复杂的相互作用。YAP对铁死亡发挥负性调节作用,促进癌细胞存活和耐药。本综述简要总结了目前对YAP通路、铁死亡以及实体肿瘤细胞和癌症干细胞中耐药机制之间相互作用的理解。我们还探讨了天然化合物单独或与抗癌疗法联合靶向YAP通路治疗耐药乳腺癌的潜力。这种方法有望提高当前治疗的有效性,并为开发新的治疗方法铺平道路。