Autophagy deficiency promotes lung metastasis of prostate cancer via stabilization of TWIST1

作者全名："Shi, Y. X.; Sun, Z. W.; Jia, D. L.; Wang, H. B."

作者地址："[Shi, Y. X.; Jia, D. L.; Wang, H. B.] Jining Med Univ, Dept Orthopaed, Affiliated Hosp, 129 Hehua Rd, Jining, Shandong, Peoples R China; [Shi, Y. X.; Jia, D. L.; Wang, H. B.] Jining Med Univ, Dept Lab Med, Affiliated Hosp, 89 Guhuai Rd, Jining, Shandong, Peoples R China; [Sun, Z. W.] Chongqing Med Univ, Inst Life Sci, 1 Yixue Yuan Rd, Chongqing, Peoples R China"

通信作者："Wang, HB (通讯作者)，Jining Med Univ, Dept Orthopaed, Affiliated Hosp, 129 Hehua Rd, Jining, Shandong, Peoples R China.; Wang, HB (通讯作者)，Jining Med Univ, Dept Lab Med, Affiliated Hosp, 89 Guhuai Rd, Jining, Shandong, Peoples R China."

来源：CLINICAL & TRANSLATIONAL ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000752740400001

JCR分区：Q3

影响因子：3.4

年份：2022

卷号：24

期号：7

开始页：1403

结束页：1412

文献类型：Article

关键词：ATG5; TWIST1; Metastasis; p62 accumulation; Phenotype crosstalk

摘要："Purpose The role of autophagy in prostate cancer metastasis remains controversial, and the effects of the autophagy-related gene ATG5 on prostate cancer metastasis are poorly understood. This study aims to explore the effects of ATG5 on prostate cancer metastasis and its molecular mechanism. Methods The metastatic characteristics of LNCaP and DU145 cells were assessed by NOD/SCID mouse experiments, western blot, transwell assay, and wound-healing assay. Double membrane autophagic vesicle observation and the adenovirus-expressing mCherry-GFP-LC3B fusion protein were used to assess the autophagic characteristics of LNCaP and DU145 cells. The role of p62 in the accumulation of TWIST1 was confirmed by western blot under different conditions. The lentivirus particles of shATG5, NOD/SCID mice experiments, western blot, transwell assay, and wound-healing assay were used to confirm the role of ATG5 in TWIST1 accumulation and prostate cancer cell metastasis. Results We identified a stabilizing effect of p62 on TWIST1 in the autophagic regulation of EMT and prostate cancer metastasis. The loss of ATG5 in DU145 cells resulted in autophagy deficiency and p62 accumulation, which stabilized TWIST1 and increased the TWIST1 level in prostate cancer cells, and eventually promoted EMT and metastasis. In comparison, LNCaP cells with regular ATG5 expression and autophagy status retained remarkable epithelial cell characteristics and had limited metastatic characteristics. Similar results were also found in wild-type LNCaP cells and LNCaP cells with stable ATG5 interference. Conclusions Our research revealed ATG5-mediated autophagy as a key mechanism that controls the metastasis of prostate cancer by regulating p62 abundance and TWIST1 stabilization."

基金机构：PhD Research Foundation of the Affiliated Hospital of Jining Medical University [2021-BS-009]

基金资助正文：This work was supported by the PhD Research Foundation of the Affiliated Hospital of Jining Medical University (2021-BS-009).