Beclin1 inhibition enhances paclitaxel‑mediated cytotoxicity in breast cancer in�vitro and in�vivo

Wu, Chenglin; Liu, Jianfei; Liu, Yan; Wang, Yu‐Xiao; Fu, Kaifei; Yu, Xiaojie; Qian, Pu; Chen, Xiu‐Xiu; Zhou, Lijun

doi:10.3892/ijmm.2019.4089

Cited by 11 publications

(14 citation statements)

References 53 publications

(71 reference statements)

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“…For instance, the suppression of Beclin1 increased TAM sensitivity in ER-positive breast cancer cells in vitro, and lower Beclin1 expression was associated with favorable outcome in patients with ER-positive breast cancer [172]. Similarly, Beclin1 inhibition enhanced paclitaxel-mediated cytotoxicity in BT-474 ER+ breast cancer cells in vitro and contributed to decreased tumor volume in a xenograft model [171], suggesting that Beclin1 protects these cells from drug-induced apoptosis. However, it is not excluded that this effect is caused by autophagy-independent functions of Beclin1.…”

Section: Autophagy Inhibitionmentioning

confidence: 96%

“…HER2 is known to inhibit autophagy by binding to Beclin1 [61], and HER2 amplification in breast cancer is often associated with BECN1 DNA copy loss [170]. Subsequent studies showed that Beclin1 exerts either a cytoprotective or cytotoxic effect depending on the molecular subtype [171]. For instance, the suppression of Beclin1 increased TAM sensitivity in ER-positive breast cancer cells in vitro, and lower Beclin1 expression was associated with favorable outcome in patients with ER-positive breast cancer [172].…”

Section: Autophagy Inhibitionmentioning

confidence: 99%

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The Multifaceted Functions of Autophagy in Breast Cancer Development and Treatment

Niklaus

Tokarchuk

Zbinden

et al. 2021

Cells

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Macroautophagy (herein referred to as autophagy) is a complex catabolic process characterized by the formation of double-membrane vesicles called autophagosomes. During this process, autophagosomes engulf and deliver their intracellular content to lysosomes, where they are degraded by hydrolytic enzymes. Thereby, autophagy provides energy and building blocks to maintain cellular homeostasis and represents a dynamic recycling mechanism. Importantly, the clearance of damaged organelles and aggregated molecules by autophagy in normal cells contributes to cancer prevention. Therefore, the dysfunction of autophagy has a major impact on the cell fate and can contribute to tumorigenesis. Breast cancer is the most common cancer in women and has the highest mortality rate among all cancers in women worldwide. Breast cancer patients often have a good short-term prognosis, but long-term survivors often experience aggressive recurrence. This phenomenon might be explained by the high heterogeneity of breast cancer tumors rendering mammary tumors difficult to target. This review focuses on the mechanisms of autophagy during breast carcinogenesis and sheds light on the role of autophagy in the traits of aggressive breast cancer cells such as migration, invasion, and therapeutic resistance.

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Section: Autophagy Inhibitionmentioning

confidence: 96%

Section: Autophagy Inhibitionmentioning

confidence: 99%

The Multifaceted Functions of Autophagy in Breast Cancer Development and Treatment

Niklaus

Tokarchuk

Zbinden

et al. 2021

Cells

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“…Furthermore, gene silencing of BECN-1 enhanced the efficiency of fasudil (a RhoA/ROCK inhibitor) to induce apoptosis in esophageal squamous cell carcinoma cells ( 46 ). Similarly, in vitro suppression of BECN1 reduces paclitaxel-mediated cell viability, colony formation, and induced apoptotic death in BT-474 and MDA-MB-231 breast cancer cells in dose- and time-dependent manners ( 47 ). Similar effects were observed in non-small cancer lung cancer (NSCLC) cells, endometrial carcinoma, nasopharyngeal carcinoma cells, and ovarian and renal cancers ( 48 – 53 ).…”

Section: Impact Of Inhibiting the Initiation And Nucleation Steps On mentioning

confidence: 99%

“…Similar effects were observed in non-small cancer lung cancer (NSCLC) cells, endometrial carcinoma, nasopharyngeal carcinoma cells, and ovarian and renal cancers ( 48 – 53 ). Interestingly, the therapeutic benefit of paclitaxel was increased in a Becn1 -targeted BT-474 xenograft mice model based on cleaved caspase-3 positive cells and inhibition of tumor growth ( 47 ).…”

Section: Impact Of Inhibiting the Initiation And Nucleation Steps On mentioning

confidence: 99%

Targeting Cytoprotective Autophagy to Enhance Anticancer Therapies

et al. 2021

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Autophagy is a highly regulated multi-step process that occurs at the basal level in almost all cells. Although the deregulation of the autophagy process has been described in several pathologies, the role of autophagy in cancer as a cytoprotective mechanism is currently well established and supported by experimental and clinical evidence. Our understanding of the molecular mechanism of the autophagy process has largely contributed to defining how we can harness this process to improve the benefit of cancer therapies. While the role of autophagy in tumor resistance to chemotherapy is extensively documented, emerging data point toward autophagy as a mechanism of cancer resistance to radiotherapy, targeted therapy, and immunotherapy. Therefore, manipulating autophagy has emerged as a promising strategy to overcome tumor resistance to various anti-cancer therapies, and autophagy modulators are currently evaluated in combination therapies in several clinical trials. In this review, we will summarize our current knowledge of the impact of genetically and pharmacologically modulating autophagy genes and proteins, involved in the different steps of the autophagy process, on the therapeutic benefit of various cancer therapies. We will also briefly discuss the challenges and limitations to developing potent and selective autophagy inhibitors that could be used in ongoing clinical trials.

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“…BECN1, an essential autophagy gene, was reported to play a pivotal role in tumor biology. For example, the knockdown of BECN1 significantly enhanced breast cancer cell sensitivity to paclitaxel through caspase-dependent apoptosis [ 44 ]. Consistently, BECN1 has been reported as an oncogene in non-small-cell lung cancer, which could enhance paclitaxel resistance through involvement in autophagy in lung cancer cells [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Hsa_circ_0020850 promotes the malignant behaviors of lung adenocarcinoma by regulating miR-326/BECN1 axis

et al. 2022

World J Surg Onc

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Background Circular RNAs (circRNAs) are a novel type of endogenous RNAs and play vital roles in lung adenocarcinoma. However, the function and underlying mechanism of circ_0020850 in lung adenocarcinoma remain unknown. Methods The levels of circ_0020850, microRNA-326 (miR-326), and Beclin1 (BECN1) were analyzed by real-time quantitative polymerase chain reaction and western blot analyses. The migration and invasion were determined by wound healing and transwell assays, respectively. Colony formation assay was used to assess cell proliferation ability. The angiogenic ability was analyzed by Matrigel angiogenesis assay. The apoptosis rate was calculated by flow cytometry assay. Dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays were conducted to confirm the interaction relationship among circ_0020850, miR-326, and BECN1. A xenograft mice model was established to assess the role of circ_0020850 in vivo. Results We found that circ_0020850 was obviously overexpressed in lung adenocarcinoma tissues and cells. Knockdown of circ_0020850 inhibited migration, invasion, proliferation, and angiogenesis but induced apoptosis in lung adenocarcinoma cells in vitro, as well as curbed tumor growth in vivo. MiR-326 was a target of circ_0020850, and knockdown of miR-326 abolished the suppression effect of circ_0020850 on the malignant behaviors of lung adenocarcinoma cells. Additionally, miR-326 could negatively regulate BECN1 expression, thereby regulating lung adenocarcinoma cell phenotypes. Importantly, circ_0020850 could directly bind to miR-326 and thus relieve miR-326-mediated inhibition on BECN1. Conclusion Circ_0020850 promoted the malignant development of lung adenocarcinoma by regulating miR-326/BECN1 axis, indicating that circ_0020850 might serve as a promising target for the diagnosis and treatment of lung adenocarcinoma patients.

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Beclin1 inhibition enhances paclitaxel‑mediated cytotoxicity in breast cancer in�vitro and in�vivo

Cited by 11 publications

References 53 publications

The Multifaceted Functions of Autophagy in Breast Cancer Development and Treatment

The Multifaceted Functions of Autophagy in Breast Cancer Development and Treatment

Targeting Cytoprotective Autophagy to Enhance Anticancer Therapies

Hsa_circ_0020850 promotes the malignant behaviors of lung adenocarcinoma by regulating miR-326/BECN1 axis

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