Autophagy is differentially induced in prostate cancer LNCaP, DU145 and PC-3 cells via distinct splicing profiles of ATG5

Ouyang, Dong-Yun; Xu, Lihui; He, Xian-Hui; Zhang, Yanting; Zeng, Longhui; Cai, Jiye; Ren, Shuai

doi:10.4161/auto.22397

Cited by 105 publications

(102 citation statements)

References 50 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…2A). This observation was not unexpected as the lack of one or two exons in ATG5 interferes with the formation of LC3-II in DU145 cells (12). Consistently, EGFP-LC3 puncta was not be observed in Tet-treated DU145 cells (Fig.…”

Section: Tetrandrine Fails To Induce Lc3 Conversion In Du145 Cellssupporting

confidence: 61%

“…Therefore, evaluation of autophagy using LC3-based It has been reported that serum starvation, CQ treatment and rapamycin treatment all failed to induce LC3-I to LC3-II conversion in DU145 cells (12). Due to the lack of functional products of ATG5, the LC3-I to LC3-II conversion is blocked (12). Therefore, the EGFP-LC3 marked autophagosomes could not be observed in DU145 cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…This alternative autophagy was characterized as the accumulation of autophagosomes without affecting LC3 conversion. Therefore, evaluation of autophagy using LC3-based It has been reported that serum starvation, CQ treatment and rapamycin treatment all failed to induce LC3-I to LC3-II conversion in DU145 cells (12). Due to the lack of functional products of ATG5, the LC3-I to LC3-II conversion is blocked (12).…”

Section: Discussionmentioning

confidence: 99%

“…Regardless of the Tet target, the present authors and other groups have previously consistently observed that Tet increases the number of autophagosomes, levels of microtubule-associated protein 1 light chain 3, type II (LC3-II) and the number of enhanced green fluorescent protein-LC3 puncta in cancer cells (1,3,9). DU145, a commonly used prostate cancer cell line for research, is different from PC-3 and LNCaP cells in terms of autophagy regulation (12). As alternative transcripts of autophagy related 5 (ATG5) lack one or two exons in DU145 cells, and this causes the autophagy pathway to be genetically impaired (12).…”

Section: Introductionmentioning

confidence: 99%

“…DU145, a commonly used prostate cancer cell line for research, is different from PC-3 and LNCaP cells in terms of autophagy regulation (12). As alternative transcripts of autophagy related 5 (ATG5) lack one or two exons in DU145 cells, and this causes the autophagy pathway to be genetically impaired (12). By contrast, DU145 cells exhibited the highest sensitivity to Tet in all of the 11 cancer cell lines that were previously tested by the authors of the present study (1), implying that impairment in autophagy may increase Tet-induced cell death.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Tetrandrine triggers an alternative autophagy in DU145 cells

2017

View full text Add to dashboard Cite

Abstract. Tetrandrine (Tet), a potent lysosomal inhibitor, blocks autophagic flux and induces cancer cell death. Previously, the present authors identified the prostate cancer cell line DU145 to exhibit high sensitivity towards Tet in 11 cancer cell lines. In the present study, autophagy in Tet-treated DU145 cells was investigated. Similar to other cell lines, such as PC-3 and 786-O cells, Tet neutralized the acidity of lysosome and blocked autophagy in DU145 cells. However, Tet failed to induce microtubule-associated protein 1 light chain 3 (LC3) conversion in DU145 cells. By contrast, it was observed by transmission electron microscopy that Tet induced an accumulation of autophagosomes in the cytoplasm. These contrasting results indicated that Tet triggered an LC3-independent autophagy in DU145 cells. Alkalizing lysosome with chloroquine enhanced Tet-induced cell death. The results of the present study indicated that detection of autophagy in tumor cells may assist in selecting lysosome inhibitors for chemotherapy treatment in prostate cancer. Introduction Tetrandrine (Tet), a natural product isolated fromStephania tetrandra, has been reported to be an anti-tumor and anti-inflammatory drug (1-8). Previously, the present authors have demonstrated that Tet induces cell death in 11 cancer cell lines (1). Tet directly neutralizes the lysosomal acidity, blocks the autophagic flux in the degradation step and causes energetic impairment, which eventually results in cell death (1). By contrast, Tet also acts as an autophagy agonist by inducing the synthesis of reactive oxygen species (3,4,9-11), indicating that Tet may function as a multi-target drug to regulate autophagy in cancer cells. Regardless of the Tet target, the present authors and other groups have previously consistently observed that Tet increases the number of autophagosomes, levels of microtubule-associated protein 1 light chain 3, type II (LC3-II) and the number of enhanced green fluorescent protein-LC3 puncta in cancer cells (1,3,9). DU145, a commonly used prostate cancer cell line for research, is different from PC-3 and LNCaP cells in terms of autophagy regulation (12). As alternative transcripts of autophagy related 5 (ATG5) lack one or two exons in DU145 cells, and this causes the autophagy pathway to be genetically impaired (12). By contrast, DU145 cells exhibited the highest sensitivity to Tet in all of the 11 cancer cell lines that were previously tested by the authors of the present study (1), implying that impairment in autophagy may increase Tet-induced cell death. In order to investigate the role of autophagy on Tet-induced cell death in DU145 cells, the ultrastructural changes following Tet treatment were observed by transmission electron microscopy (TEM). Notably, Tet treatment triggered an accumulation of autophagosomes in this cell line, indicating that alternative autophagy was involved. Materials and methodsTetrandrine and other reagents. Tet (Santa Cr uz Biotechnology, Inc., Dallas, TX, USA) was dissolved as previously described (1)....

show abstract

Section: Tetrandrine Fails To Induce Lc3 Conversion In Du145 Cellssupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Tetrandrine triggers an alternative autophagy in DU145 cells

2017

View full text Add to dashboard Cite

show abstract

Graphene Oxide Triggers Toll‐Like Receptors/Autophagy Responses In Vitro and Inhibits Tumor Growth In Vivo

Chen

Tuan

et al. 2014

Adv Healthcare Materials

105

View full text Add to dashboard Cite

Graphene oxide (GO) is a nanomaterial with burgeoning bioapplications, while autophagy is implicated in cancer therapy. Although induction of autophagy by nanomaterials is reported, the underlying signaling mechanism in cancer cells and how this implicates the potential of GO in cancer therapy remain obscure. Here, it is shown that GO itself can induce the toll-like receptors (TLRs) responses and autophagy in cancer cells and confer antitumor effects in mice. GO can be phagocytosed by CT26 colon cancer cells, simultaneously triggering autophagy as well as TLR-4 and TLR-9 signaling cascades. By dissecting the crosstalk between the TLRs and autophagy pathways, it is uncovered that the GO-activated autophagy is regulated through the myeloid differentiation primary response gene 88 (MyD88)- and TNF receptor-associated factor 6 (TRAF6)-associated TLR-4/9 signaling pathways. Injection of GO alone into immunocompetent mice bearing the CT26 colon tumors not only suppresses the tumor progression but also enhances cell death, autophagy, and immune responses within the tumor bed. These data altogether implicate the potential of GO as an effective nanomaterial for autophagy induction and cancer therapy.

show abstract

Role of alternative splicing signatures in the prognosis of glioblastoma

Xie

Dang

et al. 2019

Cancer Medicine

View full text Add to dashboard Cite

Background Increasing evidence has validated the crucial role of alternative splicing (AS) in tumors. However, comprehensive investigations on the entirety of AS and their clinical value in glioblastoma (GBM) are lacking. Methods The AS profiles and clinical survival data related to GBM were obtained from The Cancer Genome Atlas database. Univariate and multivariate Cox regression analyses were performed to identify survival‐associated AS events. A risk score was calculated, and prognostic signatures were constructed using seven different types of independent prognostic AS events, respectively. The Kaplan‐Meier estimator was used to display the survival of GBM patients. The receiver operating characteristic curve was applied to compare the predictive efficacy of each prognostic signature. Enrichment analysis and protein interactive networks were conducted using the gene symbols of the AS events to investigate important processes in GBM. A splicing network between splicing factors and AS events was constructed to display the potential regulatory mechanism in GBM. Results A total of 2355 survival‐associated AS events were identified. The splicing prognostic model revealed that patients in the high‐risk group have worse survival rates than those in the low‐risk group. The predictive efficacy of each prognostic model showed satisfactory performance; among these, the Alternate Terminator (AT) model showed the best performance at an area under the curve (AUC) of 0.906. Enrichment analysis uncovered that autophagy was the most enriched process of prognostic AS gene symbols in GBM. The protein network revealed that UBC, VHL, KCTD7, FBXL19, RNF7, and UBE2N were the core genes in GBM. The splicing network showed complex regulatory correlations, among which ELAVL2 and SYNE1_AT_78181 were the most correlated (r = −.506). Conclusions Applying the prognostic signatures constructed by independent AS events shows promise for predicting the survival of GBM patients. A splicing regulatory network might be the potential splicing mechanism in GBM.

show abstract

Autophagy is differentially induced in prostate cancer LNCaP, DU145 and PC-3 cells via distinct splicing profiles of ATG5

Cited by 105 publications

References 50 publications

Tetrandrine triggers an alternative autophagy in DU145 cells

Tetrandrine triggers an alternative autophagy in DU145 cells

Graphene Oxide Triggers Toll‐Like Receptors/Autophagy Responses In Vitro and Inhibits Tumor Growth In Vivo

Role of alternative splicing signatures in the prognosis of glioblastoma

Contact Info

Product

Resources

About