Autophagy as an emerging therapy target for ovarian carcinoma

Zhan, Lei; Zhang, Yu; Wang, Wenyan; Song, Enxue; Fan, Yijun; Li, Jun; Wei, Bing

doi:10.18632/oncotarget.13080

Cited by 48 publications

(50 citation statements)

References 101 publications

(133 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previously, the role of autophagy in cancer therapy has been proposed. It is now well accepted that in response to various chemotherapeutic drugs, radiation, and targeted therapeutics, cancer cells show large‐scale accumulation of autophagic vacuoles . It has been reported that TAM induces autophagy in tumor cells .…”

Section: Discussionmentioning

confidence: 99%

“…It is now well accepted that in response to various chemotherapeutic drugs, radiation, and targeted therapeutics, cancer cells show large-scale accumulation of autophagic vacuoles. [39][40][41] It has been reported that TAM induces autophagy in tumor cells. 26,42 Herein, Figure 3 showed that TAM increased autolysosome and the ratio of LC3II/LC3I mainly in U87 cells while potently inducing apoptosis in U251 cells.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Estrogen receptor variant ER‐α36 promotes tamoxifen agonist activity in glioblastoma cells

Zhang

et al. 2019

Cancer Science

View full text Add to dashboard Cite

Glioblastoma (GBM) is a highly infiltrative and malignant primary brain tumor. Despite aggressive therapy, patients with GBM have a dismal prognosis with median survival of approximately 1 year. Tamoxifen (TAM), a selective estrogen receptor modulator (SERM), has been used to treat GBM for many years. ER‐α36 is a novel variant of estrogen receptor‐alpha66 (ER‐α66) and can mediate cell proliferation through estrogen or anti‐estrogen signaling in different cancer cells. Previously, we found that ER‐α36 was highly expressed in GBM and was involved in the tamoxifen sensitivity of glioblastoma cells. However, the molecular mechanism responsible has not been well established. Here, we found that ER‐α36 is highly expressed in glioblastoma specimens. We further found that ER‐α36 knockdown increased sensitivity of glioblastoma U87 cells to TAM and decreased autophagy in these cells. However, ER‐α36 overexpression decreased TAM sensitivity and induced autophagy. We also established TAM‐resistant glioblastoma U251 cells by a long‐term culture in TAM‐containing medium and found that TAM‐resistant cells showed a six‐fold increase of ER‐α36 mRNA expression and elevated basal autophagy. ER‐α36 knockdown in these TAM‐resistant cells restored TAM sensitivity. In addition, we recapitulated the physiologically relevant tumor microenvironment in an integrated microfluidic device, and U87 cells were treated with a gradient of TAM. We found that ER‐α36 expression is consistent with autophagy protein P62 in a three‐dimensional microenvironment. In summary, these results indicate that ER‐α36 contributes to tamoxifen resistance in glioblastoma cells presumably through regulation of autophagy.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Estrogen receptor variant ER‐α36 promotes tamoxifen agonist activity in glioblastoma cells

Zhang

et al. 2019

Cancer Science

View full text Add to dashboard Cite

show abstract

“…Presently, autophagy is a target process in the therapy of cancer 159 and of ovarian cancer in particular. 160 With increasing recognition of the role of CAFs in carcinogenesis and progression, it is believed that targeting the metabolic cross-talk between epithelial cancer cells and CAFs could open novel therapeutic strategies to fight ovarian cancer. 161 Potential therapeutic strategies presently under investigation include, among others, inhibitors of the signaling pathways triggered by TGF-and HIF-1 , two known inducers of autophagy in CAFs (Fig.…”

Section: Concluding Remarks and Perspectivesmentioning

confidence: 99%

The metabolic cross‐talk between epithelial cancer cells and stromal fibroblasts in ovarian cancer progression: Autophagy plays a role

Thuwajit

Ferraresi

Titone

et al. 2017

Medicinal Research Reviews

View full text Add to dashboard Cite

Cancer and stromal cells, which include (cancer‐associated) fibroblasts, adipocytes, and immune cells, constitute a mixed cellular ecosystem that dynamically influences the behavior of each component, creating conditions that ultimately favor the emergence of malignant clones. Ovarian cancer cells release cytokines that recruit and activate stromal fibroblasts and immune cells, so perpetuating a state of inflammation in the stroma that hampers the immune response and facilitates cancer survival and propagation. Further, the stroma vasculature impacts the metabolism of the cells by providing or limiting the availability of oxygen and nutrients. Autophagy, a lysosomal catabolic process with homeostatic and prosurvival functions, influences the behavior of cancer cells, affecting a variety of processes such as the survival in metabolic harsh conditions, the invasive growth, the development of immune and chemo resistance, the maintenance of stem‐like properties, and dormancy. Further, autophagy is involved in the secretion and the signaling of promigratory cytokines. Cancer‐associated fibroblasts can influence the actual level of autophagy in ovarian cancer cells through the secretion of pro‐inflammatory cytokines and the release of autophagy‐derived metabolites and substrates. Interrupting the metabolic cross‐talk between cancer cells and cancer‐associated fibroblasts could be an effective therapeutic strategy to arrest the progression and prevent the relapse of ovarian cancer.

show abstract

“…In this case, promoting autophagy can inhibit the progression of ovarian cancer. Autophagy induction is closely related to the promotion of apoptosis and inhibition of proliferation in ovarian cancer [11].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of BMPER in Ovarian Cancer and the Mechanism by which It Promotes Malignant Biological Behavior in Tumor Cells

Nie

Wang

et al. 2020

BioMed Research International

View full text Add to dashboard Cite

Background. BMPER has been reported to be associated with the biological behavior of a few malignant tumors, but the mechanism is still unclear. We aimed to detect BMPER expression in ovarian epithelial tumor tissues and its effects on their biological behaviors, as well as to elucidate the possible mechanism. Methods. BMPER expression in ovarian epithelial tumor tissues was detected by immunohistochemistry. BMPER expression in ovarian cancer cell lines was inhibited via RNA interference. Changes in the malignant behaviors of ovarian cancer cells were detected by MTT, wound healing, Transwell, and flow cytometry assays. Changes in proteins in the MAPK and autophagy-related signaling pathways were detected by Western blot analysis. Results. The expression of BMPER was significantly upregulated in ovarian epithelial malignant tumors and was related to increased lymph node metastasis and lower survival rate. High BMPER expression is an independent risk factor for poor prognosis in patients. Inhibition of BMPER inhibited the proliferation, invasion, and migration of ovarian cancer cells and promoted apoptosis. In addition, BMPER downregulation decreased the expression of PCNA, Bcl-2, MMP2, and MMP9 and increased the expression of Bax. Moreover, the levels of p-ERK, p-MEK, and the autophagy-related protein p-mTOR were decreased, and Beclin 1 levels and the LC3II/I ratio were increased. Conclusions. Our findings indicated that BMPER is closely related to poor prognosis in ovarian cancer. BMPER plays a role in promoting the malignant biological behavior of tumor cells through the MAPK and autophagy-related signaling pathways.

show abstract

Autophagy as an emerging therapy target for ovarian carcinoma

Cited by 48 publications

References 101 publications

Estrogen receptor variant ER‐α36 promotes tamoxifen agonist activity in glioblastoma cells

Estrogen receptor variant ER‐α36 promotes tamoxifen agonist activity in glioblastoma cells

The metabolic cross‐talk between epithelial cancer cells and stromal fibroblasts in ovarian cancer progression: Autophagy plays a role

Overexpression of BMPER in Ovarian Cancer and the Mechanism by which It Promotes Malignant Biological Behavior in Tumor Cells

Contact Info

Product

Resources

About