Shen Hongyu, Li Liangpeng, Zhou Siying, Yu Dandan, Yang Sujin, Chen Xiu, Wang Dandan, Zhong Shanliang, Zhao Jianhua, Tang Jinhai
The Fourth Clinical School of Nanjing Medical University, Baiziting 42, Nanjing, Jiangsu, 210009, China.
Department of General Surgery, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Baiziting 42, Nanjing, Jiangsu, 210009, China.
Tumour Biol. 2016 Dec;37:15359–15370. doi: 10.1007/s13277-016-5418-y. Epub 2016 Sep 22.
A disintegrin and metalloproteinase (ADAM) family members are known to process the target membrane-bound molecules through the quick induction of their protease activities under interaction with other molecules, which have diverse roles in tissue morphogenesis and pathophysiological remodeling. Among these, ADAM17 is a membrane-bound protease that sheds the extracellular domain of various receptors or its ligands from the cell membrane and subsequently activates downstream signaling transduction pathways. Importantly, breast cancer remains a mainspring of cancer-induced death in women, and numerous regulatory pathways have been implicated in the formation of breast cancer. Substantial evidence has demonstrated that an obvious increased in ADAM17 cell surface expression has been discovered in breast cancer and was shown to be associated with mammary tumorigenesis, invasiveness, and drug resistance. Over the last decades, it has received more than its share of attention that ADAM17 plays a potential role in breast cancer, including cell proliferation, invasion, angiogenesis, apoptosis, and trastuzumab resistance. In our review, we discuss the mechanisms through which ADAM17 acts on breast cancer tumorigenesis and progression. Thus, this will provide further impetus for exploiting ADAM17 as a new target for breast cancer treatment.
已知解聚素和金属蛋白酶（ADAM）家族成员在与其他分子相互作用时，通过快速诱导其蛋白酶活性来处理靶膜结合分子，这些分子在组织形态发生和病理生理重塑中具有多种作用。其中，ADAM17是一种膜结合蛋白酶，它从细胞膜上切割各种受体或其配体的细胞外结构域，随后激活下游信号转导通路。重要的是，乳腺癌仍然是女性癌症致死的主要原因，众多调控通路与乳腺癌的形成有关。大量证据表明，在乳腺癌中已发现ADAM17细胞表面表达明显增加，且显示与乳腺肿瘤发生、侵袭性和耐药性有关。在过去几十年里，ADAM17在乳腺癌中发挥潜在作用，包括细胞增殖、侵袭、血管生成、凋亡和曲妥珠单抗耐药性，已受到了过多关注。在我们的综述中，我们讨论了ADAM17作用于乳腺癌肿瘤发生和进展的机制。因此，这将为将ADAM17开发为乳腺癌治疗的新靶点提供进一步的动力。
