An ATG5 knockout promotes paclitaxel resistance in v-Ha-ras-transformed NIH 3T3 cells

Eom, Seong Yun; Hwang, Sung‐Hee; Yeom, Hojin; Lee, Michael

doi:10.1016/j.bbrc.2019.03.197

Cited by 9 publications

(7 citation statements)

References 24 publications

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“…Further studies have demonstrated that autophagy may be associated with resistance to a variety of anti-breast cancer drugs, such as tamoxifen, Herceptin (trastuzumab), paclitaxel (PTX), and epirubicin (EPI) [81]. These results were also validated in multidrug-resistant v-Ha-ras-transformed NIH 3T3 cell studies showing that knockout of the autophagy regulatory gene, ATG5, increased PTX sensitivity [82].…”

Section: Autophagy and Multidrug Resistance (Mdr)mentioning

confidence: 93%

Triangular Relationship between p53, Autophagy, and Chemotherapy Resistance

Patel

Gewirtz

2020

IJMS

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Chemotherapy and radiation often induce a number of cellular responses, such as apoptosis, autophagy, and senescence. One of the major regulators of these processes is p53, an essential tumor suppressor that is often mutated or lost in many cancer types and implicated in early tumorigenesis. Gain of function (GOF) p53 mutations have been implicated in increased susceptibility to drug resistance, by compromising wildtype anti-tumor functions of p53 or modulating key p53 processes that confer chemotherapy resistance, such as autophagy. Autophagy, a cellular survival mechanism, is initially induced in response to chemotherapy and radiotherapy, and its cytoprotective nature became the spearhead of a number of clinical trials aimed to sensitize patients to chemotherapy. However, increased pre-clinical studies have exemplified the multifunctional role of autophagy. Additionally, compartmental localization of p53 can modulate induction or inhibition of autophagy and may play a role in autophagic function. The duality in p53 function and its effects on autophagic function are generally not considered in clinical trial design or clinical therapeutics; however, ample pre-clinical studies suggest they play a role in tumor responses to therapy and drug resistance. Further inquiry into the interconnection between autophagy and p53, and its effects on chemotherapeutic responses may provide beneficial insights on multidrug resistance and novel treatment regimens for chemosensitization.

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Section: Autophagy and Multidrug Resistance (Mdr)mentioning

confidence: 93%

Triangular Relationship between p53, Autophagy, and Chemotherapy Resistance

Patel

Gewirtz

2020

IJMS

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“…It has been shown that knocking down ATG5 in paclitaxel-resistant cells causes a G2/M arrest and makes cells susceptible to paclitaxel-induced necrosis [524]. Another study showed that direct knockdown of ATG5 increased paclitaxel resistance in Ras-NIH 3T3 (v-Ha-ras-transformed NIH 3T3) cells by reducing the frequency of early apoptotic cells [525]. Direct control of beclin-1 (ATG6) is also critical in the development of drug resistance.…”

Section: Autophagy Acts As a Chemotherapy Resistance Machinery In The...mentioning

confidence: 99%

Chemotherapy Resistance: Role of Mitochondrial and Autophagic Components

Bahar

Han

Kim

et al. 2022

Cancers

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Cancer chemotherapy resistance is one of the most critical obstacles in cancer therapy. One of the well-known mechanisms of chemotherapy resistance is the change in the mitochondrial death pathways which occur when cells are under stressful situations, such as chemotherapy. Mitophagy, or mitochondrial selective autophagy, is critical for cell quality control because it can efficiently break down, remove, and recycle defective or damaged mitochondria. As cancer cells use mitophagy to rapidly sweep away damaged mitochondria in order to mediate their own drug resistance, it influences the efficacy of tumor chemotherapy as well as the degree of drug resistance. Yet despite the importance of mitochondria and mitophagy in chemotherapy resistance, little is known about the precise mechanisms involved. As a consequence, identifying potential therapeutic targets by analyzing the signal pathways that govern mitophagy has become a vital research goal. In this paper, we review recent advances in mitochondrial research, mitophagy control mechanisms, and their implications for our understanding of chemotherapy resistance.

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“…In vivo short hairpin RNA‐mediated knockdown of ATG5 induces chemoresistance in breast cancer cells, accelerating tumor relapse 103 . Knockdown of ATG5 promotes paclitaxel (a chemotherapy medication) resistance in Ras‐transformed 3T3 cells by reducing the number of early apoptotic cells 104 . Thus, it can be speculated that ATG5 negatively regulates chemoresistance via inducing autophagy.…”

Section: Roles Of Atg5 In Various Human Diseasesmentioning

confidence: 99%

“…103 Knockdown of ATG5 promotes paclitaxel (a chemotherapy medication) resistance in Ras-transformed 3T3 cells by reducing the number of early apoptotic cells. 104 Thus, it can be speculated that ATG5 negatively regulates chemoresistance via inducing autophagy. Probably, in such cases, autophagy induces apoptosis via an unknown mechanism.…”

Section: Atg5 In Autophagy Apoptosis and Cancer Progressionmentioning

confidence: 99%

ATG5: A central autophagy regulator implicated in various human diseases

Changotra

Kaur

Yadav

et al. 2022

Cell Biochemistry & Function

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Autophagy, an intracellular conserved degradative process, plays a central role in the renewal/recycling of a cell to maintain the homeostasis of nutrients and energy within the cell. ATG5, a key component of autophagy, regulates the formation of the autophagosome, a hallmark of autophagy. ATG5 binds with ATG12 and ATG16L1 resulting in E3 like ligase complex, which is necessary for autophagosome expansion. Available data suggest that ATG5 is indispensable for autophagy and has an imperative role in several essential biological processes. Moreover, ATG5 has also been demonstrated to possess autophagy‐independent functions that magnify its significance and therapeutic potential. ATG5 interacts with various molecules for the execution of different processes implicated during physiological and pathological conditions. Furthermore, ATG5 genetic variants are associated with various ailments. This review discusses various autophagy‐dependent and autophagy‐independent roles of ATG5, highlights its various deleterious genetic variants reported until now, and various studies supporting it as a potential drug target.

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An ATG5 knockout promotes paclitaxel resistance in v-Ha-ras-transformed NIH 3T3 cells

Cited by 9 publications

References 24 publications

Triangular Relationship between p53, Autophagy, and Chemotherapy Resistance

Triangular Relationship between p53, Autophagy, and Chemotherapy Resistance

Chemotherapy Resistance: Role of Mitochondrial and Autophagic Components

ATG5: A central autophagy regulator implicated in various human diseases

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