The p53/p21 Complex Regulates Cancer Cell Invasion and Apoptosis by Targeting Bcl-2 Family Proteins

Kim, Eun Mi; Jung, Chan-Hun; Kim, Jong-Doo; Hwang, Sang‐Gu; Park, Jong Kuk; Um, Hong‐Duck

doi:10.1158/0008-5472.can-16-2098

Cited by 169 publications

(114 citation statements)

References 39 publications

(53 reference statements)

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“…Simultaneously, nuclear p53 augments the pool of BAX molecules via executing transcription of BAX 147 . The inhibitory role of p21 in the regulation of BCL-w-dependent lung cancer, colon cancer, and neuroblastoma cell invasion has been demonstrated in addition to p53 149 . Although p53 and p21 can bind to BCL-w independently, the triple p53/p21/BCL-w complex is required for BAX release from BCL-w and suppression of cell invasion (Fig.…”

Section: Role Of Bcl-w In Migratory and Invasive Potentials Of Cancermentioning

confidence: 99%

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BCL-w: apoptotic and non-apoptotic role in health and disease

Hartman

Czyż

2020

Cell Death Dis

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The BCL-2 family of proteins integrates signals that trigger either cell survival or apoptosis. The balance between prosurvival and pro-apoptotic proteins is important for tissue development and homeostasis, while impaired apoptosis contributes to several pathologies and can be a barrier against effective treatment. BCL-w is an anti-apoptotic protein that shares a sequence similarity with BCL-X L , and exhibits a high conformational flexibility. BCL-w level is controlled by a number of signaling pathways, and the repertoire of transcriptional regulators largely depends on the cellular and developmental context. As only a few disease-relevant genetic alterations of BCL2L2 have been identified, increased levels of BCL-w might be a consequence of abnormal activation of signaling cascades involved in the regulation of BCL-w expression. In addition, BCL-w transcript is a target of a plethora of miRNAs. Besides its originally recognized pro-survival function during spermatogenesis, BCL-w has been envisaged in different types of normal and diseased cells as an anti-apoptotic protein. BCL-w contributes to survival of senescent and drug-resistant cells. Its non-apoptotic role in the promotion of cell migration and invasion has also been elucidated. Growing evidence indicates that a high BCL-w level can be therapeutically relevant in neurodegenerative disorders, neuron dysfunctions and after small intestinal resection, whereas BCL-w inhibition can be beneficial for cancer patients. Although several drugs and natural compounds can bi-directionally affect BCL-w level, agents that selectively target BCL-w are not yet available. This review discusses current knowledge on the role of BCL-w in health, non-cancerous diseases and cancer.

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Section: Role Of Bcl-w In Migratory and Invasive Potentials Of Cancermentioning

confidence: 99%

“…Although p53 and p21 can bind to BCL-w independently, the triple p53/p21/BCL-w complex is required for BAX release from BCL-w and suppression of cell invasion (Fig. 3) 149 .…”

Section: Role Of Bcl-w In Migratory and Invasive Potentials Of Cancermentioning

confidence: 99%

BCL-w: apoptotic and non-apoptotic role in health and disease

Hartman

Czyż

2020

Cell Death Dis

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“…This assumption is corroborated by the observed decrease in ΔΨm, a wallmark in p53 mediated induction of apoptosis. For cell cycle arrest, p53 exerts its effects through cyclin-dependent kinase (CDK) inhibitor p21, leading to cell cycle arrest (Kim et al, 2017). Cell cycle analysis showed that PSC-hex induced cell cycle arrest at the G2/M phase, suggesting a blockage of cell proliferation of the HCT116 wt , which might be regulated by p53 by activating p21.…”

Section: Intrinsic Signaling Pathway Modulated Apoptosis In Hct116 Wtmentioning

confidence: 99%

Apoptosis induction by Pleurotus sajor-caju (Fr.) Singer extracts on colorectal cancer cell lines

Finimundy

Abreu

Bonetto

et al. 2018

Food and Chemical Toxicology

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Pleurotus sajor-caju (PSC) is an edible mushroom used in food supplements, presenting antitumor properties through induction of cell death pathways. The PSC potential against colorectal cancer was analyzed by exposing HCT116 cells to different PSC extracts. The PSC n-hexane extract (PSC-hex) showed the highest cytotoxicity effect (IC value 0.05 mg/mL). The observed cytotoxicity was then associated to apoptosis-promoting and cell cycle-arrest pathways. PSC-hex was able to induce apoptosis related to breakdown of mitochondrial membrane potential and ROS generation. The absence of cytotoxicity in HTC116 and HTC116 cells, alongside with an increase in p53, Bax and Caspase-3 expression, and decrease in Bcl-2 expression, supports that the pro-apoptotic effect is probably induced through a p53 associated pathway. PSC-hex induced cell cycle arrest at G2/M in HCT116 without cytotoxicity in HTC116 cells. These findings suggest that a p21/p53 cell cycle regulation pathway is probably disrupted by compounds present on PSC-hex. Identification of the major components was then performed with ergosta-5,7,22-trien-3β-ol representing 30.6% of total weight. In silico docking studies of ergosta-5,7,22-trien-3β against Bcl-2 were performed and results show a credible interaction with the Bcl-2 hydrophobic cleft. The results show that PSC-hex can be used as supplementary food for adjuvant therapy in colorectal carcinoma.

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“…p53 causes apoptosis via regulating the expression, cellular localization, and activity of key effectors of the apoptotic process . p21, a well‐described transcriptional target of p53, regulates cell invasion and death by targeting Bcl‐2 proteins through forming p53/p21 complex . While the pro‐apoptotic Bax gene is a direct target of p53, the overexpression of p53 in p53‐null cells diminish Bcl‐2 expression .…”

Section: Discussionmentioning

confidence: 99%

Heterogeneous expression and biological function of SOX18 in osteosaroma

Zhu

Yang

et al. 2018

J of Cellular Biochemistry

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Osteosaroma (OS) is a primary bone malignancy and is associated with high morbidity. Sex determining region Y-box 18 (SOX18) is identified overexpressed in OS. However, the molecular mechanism underlying the biological function of SOX18 in OS is still unclear. The aim of the current study was to determine the SOX18 expression in patients with OS and its effect on tumor cell malignant phenotypes. Our results showed that SOX18 was overexpressed in OS patients from both E-MEXP-3628 database and independent samples from our hospital and in OS cell lines. SOX18 silencing significantly induced G0-G1 phase cell cycle arrest and apoptosis and inhibited U-2OS cell migration and invasion and cell growth both in vitro and in vivo. However, SOX18 overexpression remarkably promoted 143B cell proliferation, migration and invasion and inhibited cell cycle arrest and apoptosis. The protein expression levels of p53, p21, Bax, Bcl-2, and Caspase-3 were also regulated by SOX18. Moreover, SOX18 was found negative correlated with the expression of HERC1, HER2, HERC3, HERC4, HERC5, and HERC6 in OS patients and in OS cells, with the most significant correlation detected in HERC2 expression, which was following found interacted with SOX18 in OS cells. Taken together, our results suggest that SOX18 is overexpressed in OS and plays an important role in proliferation, apoptosis, migration and invasion of OS cells, and may provide a novel and promising thera-peutic strategy for OS.

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The p53/p21 Complex Regulates Cancer Cell Invasion and Apoptosis by Targeting Bcl-2 Family Proteins

Cited by 169 publications

References 39 publications

BCL-w: apoptotic and non-apoptotic role in health and disease

BCL-w: apoptotic and non-apoptotic role in health and disease

Apoptosis induction by Pleurotus sajor-caju (Fr.) Singer extracts on colorectal cancer cell lines

Heterogeneous expression and biological function of SOX18 in osteosaroma

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