MUC15 inhibits cancer metastasis via PI3K/AKT signaling in renal cell carcinoma

Patients with renal cell carcinoma (RCC) often develop distant metastasis and the specific molecular mechanism remains poorly understood. In our study, we demonstrated that MUC15, a subtype of mucins family, could suppress the progression of RCC by inhibiting PI3K/AKT signaling. Firstly, we observed...

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Bibliographic Details
Published in:Cell death & disease 2020-05, Vol.11 (5), p.336-336, Article 336
Main Authors: Yue, Yangyang, Hui, Ke, Wu, Shiqi, Zhang, Mengzhao, Que, Taotao, Gu, Yanan, Wang, Xinyang, Wu, Kaijie, Fan, Jinhai
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
13/1
13/106
13/109
13/51
13/89
13/95
59/5
631/67/1857
631/80/84/2336
64/60
AKT protein
Animals
Antibodies
Biochemistry
Biomedical and Life Sciences
Carcinoma, Renal Cell - genetics
Carcinoma, Renal Cell - pathology
Cell Biology
Cell Culture
Cell Line, Tumor
Cell Movement - genetics
Down-Regulation - genetics
Female
Gelatinase A
Gelatinase B
Gene expression
Gene Expression Regulation, Neoplastic
Humans
Immunology
Kidney cancer
Kidney Neoplasms - genetics
Kidney Neoplasms - pathology
Life Sciences
Matrix Metalloproteinases - metabolism
Metastases
Metastasis
Mice, Inbred BALB C
Mice, Nude
mRNA
Mucin
Mucins - genetics
Mucins - metabolism
Neoplasm Invasiveness
Neoplasm Metastasis
Phosphatidylinositol 3-Kinases - metabolism
Phosphorylation
Proto-Oncogene Proteins c-akt - metabolism
Renal cell carcinoma
Signal Transduction
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Description
Summary:Patients with renal cell carcinoma (RCC) often develop distant metastasis and the specific molecular mechanism remains poorly understood. In our study, we demonstrated that MUC15, a subtype of mucins family, could suppress the progression of RCC by inhibiting PI3K/AKT signaling. Firstly, we observed that MUC15 was notably decreased in RCC compared to normal tissue. Furthermore, we showed that MUC15 could negatively modulate the migration and invasion of RCC in vitro and in vivo. Mechanistically, we found that knocking-down of MUC15 could active the PI3K/AKT signaling by increasing the AKT phosphorylation and subsequently increase the mRNA and protein expression of MMP2 and MMP9. Interruption of the AKT pathway with the specific inhibitor LY294002 could reverse the expression of MMPs. Therefore, our study clarify the novel function of MUC15 in RCC, which may provide a new sight to diagnose and prevent RCC metastasis.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-020-2518-9