RRC ID |
65163
|
著者 |
Maimaiti M, Sakamoto S, Sugiura M, Kanesaka M, Fujimoto A, Matsusaka K, Xu M, Ando K, Saito S, Wakai K, Imamura Y, Nakayama K, Kanai Y, Kaneda A, Ikehara Y, Ikeda JI, Anzai N, Ichikawa T.
|
タイトル |
The heavy chain of 4F2 antigen promote prostate cancer progression via SKP-2.
|
ジャーナル |
Sci Rep
|
Abstract |
The 4F2 cell-surface antigen heavy chain (4F2hc) forms a heterodimeric complex with L-type amino acid transporter 1 (LAT1) and transports large neutral essential amino acids. However, in contrast to the traditional role of LAT1 in various cancers, the role of 4F2hc has largely remained unknown. The role of 4F2hc in prostate cancer was studied. Treatment of C4-2 cells with si4F2hc was found to suppress cellular growth, migratory and invasive abilities, with this effect occurring through the cell cycle, with a significant decrease in S phase and a significant increase in G0/G1 phase, suggesting cell cycle arrest. In addition, it was proven by RNA seq that the key to 4F2hc's impact on cancer is SKP2. si4F2hc upregulates the protein expression of cyclin-dependent kinase inhibitors (P21cip1, P27kip1) through the downstream target SKP2. Furthermore, the expression of 4F2hc and LAT1 in prostate cancer cells suggests the importance of 4F2hc. Multivariate analysis showed that high 4F2hc expression was an independent prognostic factor for progression-free survival (HR 11.54, p = 0.0357). High 4F2hc was related to the clinical tumour stage (p = 0.0255) and Gleason score (p = 0.0035). Collectively, 4F2hc contributed significantly to prostate cancer (PC) progression. 4F2hc may be a novel marker and therapeutic target in PC.
|
巻・号 |
11(1)
|
ページ |
11478
|
公開日 |
2021-6-1
|
DOI |
10.1038/s41598-021-90748-9
|
PII |
10.1038/s41598-021-90748-9
|
PMID |
34075107
|
PMC |
PMC8169706
|
MeSH |
Cell Line, Tumor
Fusion Regulatory Protein 1, Heavy Chain / genetics
Fusion Regulatory Protein 1, Heavy Chain / metabolism*
G1 Phase*
Gene Expression Regulation, Neoplastic
Humans
Male
Neoplasm Proteins / genetics
Neoplasm Proteins / metabolism*
Prostatic Neoplasms / genetics
Prostatic Neoplasms / metabolism*
RNA, Small Interfering / genetics
RNA, Small Interfering / pharmacology
Resting Phase, Cell Cycle*
S-Phase Kinase-Associated Proteins / genetics
S-Phase Kinase-Associated Proteins / metabolism*
|
IF |
3.998
|
リソース情報 |
ヒト・動物細胞 |
DU145(RCB2143) |