Department of Entomology and MOA Key Laboratory for Monitory and Green Control of Crop Pest, China Agricultural University, Beijing 100193, China.
Department of Entomology and MOA Key Laboratory for Monitory and Green Control of Crop Pest, China Agricultural University, Beijing 100193, China
Biol Open. 2020 Mar 24;9(3):bio048850. doi: 10.1242/bio.048850.
Cancer cell metastasis is a leading cause of mortality in cancer patients. Therefore, revealing the molecular mechanism of cancer cell invasion is of great significance for the treatment of cancer. In human patients, the hyperactivity of transcription factor Spalt-like 4 (SALL4) is sufficient to induce malignant tumorigenesis and metastasis. Here, we found that when ectopically expressing the homologue () or human in , epithelial cells delaminated basally with penetration of the basal lamina and degradation of the extracellular matrix, which are essential properties of cell invasion. Further assay found that / promoted cell invasion via dMyc-JNK signaling. Inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway through suppressing , or can achieve suppression of cell invasion. Moreover, expression of , a suppressor of JNK signaling, dramatically blocked cell invasion induced by / in the wing disc. These findings reveal a conserved role of / in invasive cell movement and link the crucial mediator of tumor invasion, the JNK pathway, to SALL4-mediated cancer progression.This article has an associated First Person interview with the first author of the paper.
癌细胞转移是癌症患者死亡的主要原因。因此，揭示癌细胞侵袭的分子机制对于癌症的治疗具有重要意义。在人类患者中，转录因子 Spalt-like 4（SALL4）的过度活跃足以诱导恶性肿瘤发生和转移。在这里，我们发现当异位表达同源物（）或人（）时，上皮细胞从基底膜脱落，并穿透基底膜和降解细胞外基质，这是细胞侵袭的必要特性。进一步的实验发现，/ 通过 dMyc-JNK 信号通路促进细胞侵袭。通过抑制 c-Jun N-末端激酶（JNK）信号通路，通过抑制，或，可以实现对细胞侵袭的抑制。此外，JNK 信号通路的抑制剂，JNK 信号通路的关键介质，表达，可显著阻断/诱导的 wing disc 细胞侵袭。这些发现揭示了/在侵袭性细胞运动中的保守作用，并将肿瘤侵袭的关键介质 JNK 通路与 SALL4 介导的癌症进展联系起来。本文有与论文第一作者的相关第一人称访谈。
