The International Journal of Biochemistry & Cell Biology ( IF 4 ) Pub Date : 2020-06-21 , DOI: 10.1016/j.biocel.2020.105795 Haiying Zou 1 , Bing Wen 1 , Run-Liu Li 1 , Xiu-Hui Zhan 1 , Ji-Wei Jiao 1 , Lian-Di Liao 2 , Bing-Li Wu 1 , Wen-Ming Xie 3 , Li-Yan Xu 2 , En-Min Li 1
Lysyl oxidase-like 2 (LOXL2) is a member of the lysyl oxidase (LOX) family that contributes to tumor cell metastasis. Our previous data identified two splice variants of LOXL2 (i.e., LOXL2 Δ72 and Δ13) in esophageal squamous cell carcinoma (ESCC) cells that increased cell invasiveness and migration but had lower LOX activities than wild-type LOXL2 (LOXL2 WT). We generated a series of LOXL2 deletion mutants with different deleted biochemical domains and examined the relationship between the cell migration abilities and catalytic activities, as well as subcellular locations, of these deletion mutants compared with LOXL2 WT in ESCC cells to explore the mechanism of LOXL2-driven ESCC cell migration. Our results indicated that the deletion mutants of LOXL2 had impaired deamination enzymatic activity; LOXL2 ΔSRCR4, which lacks the fourth scavenger receptor cysteine-rich (SRCR) domain, had lower enzymatic activity; and LOXL2 Y689F had no catalytic activity compared with LOXL2 WT. However these two mutants stimulated greater cellular migration than LOXL2 WT. Furthermore, the degree of cell migration promoted by LOXL2 ΔLO (in which the LOX-like domain was deleted) was higher than that of LOXL2 WT, and LOXL2 ΔSRCR3, which does not have the third SRCR domain, had lower LOX activity and cellular migration ability than LOXL2 WT. These results suggested that LOXL2 promotes ESCC cell migration independent of catalytic activity.
中文翻译:
像赖氨酰氧化酶样2促进食管鳞状细胞癌细胞迁移独立于催化活性。
类赖氨酰氧化酶(LOXL2)是赖氨酰氧化酶(LOX)家族的成员,有助于肿瘤细胞转移。我们以前的数据确定了食管鳞状细胞癌(ESCC)细胞中LOXL2的两个剪接变体(即LOXL2Δ72和Δ13),其细胞侵袭性和迁移增加,但LOX活性低于野生型LOXL2(LOXL2 WT)。我们生成了一系列具有不同缺失生化结构域的LOXL2缺失突变体,并与ESXL细胞中的LOXL2 WT相比,研究了这些缺失突变体的细胞迁移能力和催化活性以及亚细胞位置之间的关系,以探索LOXL2的机制。驱动ESCC细胞迁移。我们的结果表明,LOXL2的缺失突变体损害了脱氨酶活性。LOXL2ΔSRCR4,缺乏第四个清道夫受体富含半胱氨酸(SRCR)域,具有较低的酶活性。与LOXL2 WT相比,LOXL2 Y689F没有催化活性。但是,这两个突变体比LOXL2 WT刺激的细胞迁移更大。此外,LOXL2ΔLO(其中删除了LOX样结构域)促进的细胞迁移程度高于LOXL2 WT,而没有第三个SRCR域的LOXL2ΔSRCR3具有较低的LOX活性和细胞迁移能力比LOXL2 WT高。这些结果表明LOXL2促进ESCC细胞迁移独立于催化活性。LOXL2ΔLO(其中删除了LOX样结构域)促进的细胞迁移程度高于LOXL2 WT,而没有第三个SRCR域的LOXL2ΔSRCR3具有较低的LOX活性和细胞迁移能力LOXL2 WT。这些结果表明LOXL2促进ESCC细胞迁移独立于催化活性。LOXL2ΔLO(其中删除了LOX样结构域)促进的细胞迁移程度高于LOXL2 WT,而没有第三个SRCR域的LOXL2ΔSRCR3具有较低的LOX活性和细胞迁移能力LOXL2 WT。这些结果表明LOXL2促进ESCC细胞迁移独立于催化活性。