ADAM17是“脱粒蛋白和金属蛋白酶”（ADAM）家族的一员，通过切割转膜底物，包括表皮生长因子受体（EGFR）配体，如转化生长因子(TGF)-α和Epiregulin (EREG)，来控制重要的细胞功能。几个ADAM17的底物与肿瘤发生和肿瘤生长有关。我们提出了证据表明，磷脂酰丝氨酸（PS）的表面暴露是ADAM17发挥脱落活性的关键。Scramblase Xkr8对于磷酸钙独立性暴露在细胞凋亡中的PS至关重要。Xkr8可以被caspase-3和激酶双重激活。在这项研究中，我们研究了Xkr8是否会在凋亡和非凋亡条件下调节ADAM17的活性。在HEK293T细胞中过表达Xkr8显著增加了caspase依赖性和PMA诱导的EREG和TGF-α的释放。相反，通过siRNA介导的Xkr8下调在结直肠Caco-2癌细胞中导致凋亡诱导后PS外翻的减少，这伴随着内源性表达的EREG的减少和细胞存活的减少。我们得出结论，Xkr8与传统的扰流素一样，具有上调ADAM脱落酶功能的倾向。生长因子的解放可以在通向凋亡细胞的途径上起到拯救功能。

ADAM17, a prominent member of the "Disintegrin and Metalloproteinase" (ADAM) family, controls vital cellular functions through the cleavage of transmembrane substrates, including epidermal growth factor receptor (EGFR) ligands such as transforming growth factor (TGF)-alpha and Epiregulin (EREG). Several ADAM17 substrates are relevant to oncogenesis and tumor growth. We have presented evidence that surface exposure of phosphatidylserine (PS) is pivotal for ADAM17 to exert sheddase activity. The scramblase Xkr8 is instrumental for calcium-independent exposure of PS in apoptotic cells. Xkr8 can be dually activated by caspase-3 and by kinases. In this investigation, we examined whether Xkr8 would modulate ADAM17 activity under apoptotic and non-apoptotic conditions. Overexpression of Xkr8 in HEK293T cells led to significantly increased caspase-dependent as well as PMA-induced release of EREG and TGF-alpha. Conversely, siRNA-mediated downregulation of Xkr8 in colorectal Caco-2 cancer cells led to decreased PS externalization upon induction of apoptosis, which was accompanied by reduced shedding of endogenously expressed EREG and reduced cell survival. We conclude that Xkr8 shares with conventional scramblases the propensity to upmodulate the ADAM-sheddase function. Liberation of growth factors could serve a rescue function in cells on the pathway to apoptotic death.