Abstract
Objective To investigate whether the liver regeneration phosphatase 3 (PRL-3) promotes invasion and metastasis of colorectal cancer cells (CRCs) through tumor associated macrophage (TAM). Methods We selected LoVo cells to construct PRL-3-overexpression lines (LoVo-P) and HT29 cells (HT29-P) as the knockdown groups. After co-culture with LoVo-P, LoVo-NC, HT29-NC and HT29-P respectively, we performed Western blotting to identify the activation of mitogen-activated protein kinase (MAPK) pathway in TAMs. Meanwhile, Transwell assays were carried out before and after suppressing MAPK pathway in TAMs. Besides, immunohistochemistry was used to confirm the status of MAPK in xenografts of mice injected with cells mentioned above. Results Western blot showed that the interaction between PRL-3 and TAM activated MAPK pathways in TAMs promoting EMT in CRCsand upregulated the expression of IL-6 and IL-8.LoVo-P increased by a triple expression of p-JNK and double of p-ERK than LoVo-NC (P<0.05). In terms of HT29, the levels of p-JNK and p-ERK rised to 3 folds and 1.3 folds (P<0.05). Also, transwell assays showed that cell invasion and migration were enhanced with high levels of PRL-3. In LoVo, the number of migrating cells of LoVo-P vesusLoVo-NC was [268±22 vs. 129±12], and HT29-NC vesus HT29-P was [298±19 vs. 152±14](P<0.05). Results of immunohistochemistry were consistent with those in Western blot, which showed LoVo [p-JNK: 82%/20%, p-ERK: 83%/16%] and HT29 [p-JNK: 81%: 21%, p-ERK: 76%/16%](P<0.05). Conclusion PRL-3 promotes invasion and metastasis of CRCs through EMT by initiating MAPK pathways in TAMs. Key words: Colorectal cancer; Liver regeneration phosphatase 3; Tumor-associated macrophages; Phosphorylation
Published Version
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