Emerging Roles of C-Myc in Cancer Stem Cell-Related Signaling and Resistance to Cancer Chemotherapy: A Potential Therapeutic Target Against Colorectal Cancer

Elbadawy, Mohamed; Usui, Tatsuya; Yamawaki, Hideyuki; Sasaki, Kenji

doi:10.3390/ijms20092340

Cited by 201 publications

(163 citation statements)

References 133 publications

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“…TaTDRL encodes a bHLH conserved domain at the C-terminal (295-344 aa), which localized to the nucleus and displayed transcriptional activation activity. MYC class transcription factors regulate genes involved in growth, cell cycle, signaling, and adhesion [19,20]. In generally, the carboxyl terminus of MYC family members contains a bHLH leucine zipper motif (bHLH-Zip), which has DNA-binding activity and is proposed to form homodimers or heterodimers with MYC-associated factor X (MAX) proteins via their bHLH domain [21,22].…”

Section: Structure and Localization Of The Tatdr-like Genementioning

confidence: 99%

Isolation and Identification of a TaTDR-Like Wheat Gene Encoding a bHLH Domain Protein, Which Negatively Regulates Chlorophyll Biosynthesis in Arabidopsis

Xia¹,

Li²,

Wang³

et al. 2020

IJMS

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Chlorophyll biosynthesis plays a vital role in chloroplast development and photosynthesis in plants. In this study, we identified an orthologue of the rice gene TDR (Oryza sativa L., Tapetum Degeneration Retardation) in wheat (Triticum aestivum L.) called TaTDR-Like (TaTDRL) by sequence comparison. TaTDRL encodes a putative 557 amino acid protein with a basic helix-loop-helix (bHLH) conserved domain at the C-terminal (295-344 aa). The TaTDRL protein localised to the nucleus and displayed transcriptional activation activity in a yeast hybrid system. TaTDRL was expressed in the leaf tissue and expression was induced by dark treatment. Here, we revealed the potential function of TaTDRL gene in wheat by utilizing transgenic Arabidopsis plants TaTDRL overexpressing (TaTDRL-OE) and TaTDRL-EAR (EAR-motif, a repression domain of only 12 amino acids). Compared with wild-type plants (WT), both TaTDRL-OE and TaTDRL-EAR were characterized by a deficiency of chlorophyll. Moreover, the expression level of the chlorophyll-related gene AtPORC (NADPH:protochlorophyllide oxidoreductase C) in TaTDRL-OE and TaTDRL-EAR was lower than that of WT. We found that TaTDRL physically interacts with wheat Phytochrome Interacting Factor 1 (PIF1) and Arabadopsis PIF1, suggesting that TaTDRL regulates light signaling during dark or light treatment. In summary, TaTDRL may respond to dark or light treatment and negatively regulate chlorophyll biosynthesis by interacting with AtPIF1 in transgenic Arabidopsis.

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Section: Structure and Localization Of The Tatdr-like Genementioning

confidence: 99%

Isolation and Identification of a TaTDR-Like Wheat Gene Encoding a bHLH Domain Protein, Which Negatively Regulates Chlorophyll Biosynthesis in Arabidopsis

Xia¹,

Li²,

Wang³

et al. 2020

IJMS

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“…Molecular targeted therapies aimed at c‐Myc that interfere with c‐Myc synthesis, stability, and transcriptional activity have emerged as effective cancer treatments . It has been reported that c‐Myc could be regulated by CaMK II to facilitate cancer cell proliferation . Moreover, high expression of CaMK II was found in several cancers .…”

Section: Discussionmentioning

confidence: 99%

“…21 It has been reported that c-Myc could be regulated by CaMK II to facilitate cancer cell proliferation. 14…”

Section: Discussionmentioning

confidence: 99%

“…c‐Myc directly induces the transcription of genes encoding glycolytic enzymes, including HK‐II, LDHA, PGK1 and GLUTs . Numerous studies have demonstrated the importance of this metabolic reprogramming in cancer cells . Moreover, it was reported that c‐Myc can be regulated by CaMK II to facilitate cancer cell proliferation …”

Section: Introductionmentioning

confidence: 99%

“…7,8 Numerous studies have demonstrated the importance of this metabolic reprogramming in cancer cells. [9][10][11][12][13][14] Moreover, it was reported that c-Myc can be regulated by CaMK II to facilitate cancer cell proliferation. 15 Ketamine is often used for cancer pain relief in clinical settings.…”

mentioning

confidence: 99%

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Ketamine inhibits aerobic glycolysis in colorectal cancer cells by blocking the NMDA receptor‐CaMK II‐c‐Myc pathway

Duan

Qing

2020

Clin Exp Pharma Physio

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Aerobic glycolysis plays a crucial role in cancer progression. Ketamine is often used for cancer pain relief in clinical settings. Moreover, ketamine inhibits proliferation and induces apoptosis in many cancer cell types. However, the anti‐tumour mechanism of ketamine is still poorly understood. In the present study, we survey whether and how ketamine inhibits aerobic glycolysis in colon cancer cells. Glycolysis of colon cancer cells was determined by detecting the extracellular acidification rate in HT29 and SW480 cells. Quantitative real‐time PCR was employed to determine mRNA expression. Calcium levels were detected with a Fluo‐3 AM fluorescence kit. Micro‐positron emission tomography/computed tomography (microPET/CT) imaging was employed to assess glycolysis in the tumours of the xenograft model. Ketamine treatment inhibited colon cancer cell viability and migration in HT29 and SW480 cells. Moreover, ketamine decreased aerobic glycolysis and decreased the expression of glycolysis‐related proteins in HT29 and SW480 cells. MicroPET/CT demonstrated that ketamine decreased 18F‐FDG uptake in the xenograft model. In addition, ketamine inhibited c‐Myc expression and CaMK II phosphorylation and decreased calcium levels. Further, dizocilpine (an NMDAR inhibitor), and KN93 (a CaMK II inhibitor), decreased CaMK II phosphorylation, c‐Myc expression, and cancer cell glycolysis; these results were similar to those with ketamine treatment. Furthermore, the anti‐tumour effect of ketamine was counteracted by rapastinel (an NMDAR activator). Ketamine inhibited aerobic glycolysis in colon cancer cells probably by blocking the NMDA receptor‐CaMK II‐c‐Myc pathway, thus attenuating colon cancer cell viability and migration.

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FUBP1 promotes colorectal cancer stemness and metastasis via DVL1‐mediated activation of Wnt/β‐catenin signaling

et al. 2021

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Distant metastasis is, unfortunately, the leading cause of death in colorectal cancer (CRC). Approximately 50% of CRC patients develop liver metastases, while 10-30% of patients develop pulmonary metastases. The occurrence of metastasis is considered to be almost exclusively driven by cancer stem cells (CSCs) formation. However, the key molecules that confer the transformation to stem cells in CRC, and subsequent metastasis, remain unclear. Far upstream element-binding protein 1 (FUBP1), a transcriptional regulator of c-Myc, was screened in CSCs of CRC by mass spectrometry and was examined by immunohistochemistry in a cohort of CRC tissues. FUBP1 was upregulated in 85% of KRAS-mutant and 25% of wild-type CRC patients. Further, whether in KRAS-mutant or wild-type patients, elevated FUBP1 was positively correlated with CRC lymph node metastasis and clinical stage, and negatively associated with overall survival. Overexpression of FUBP1 significantly enhanced CRC cell migration, invasion, tumor sphere formation, and CD133 and ALDH1 expression in vitro, and tumorigenicity in vivo. Mechanistically, FUBP1 promoted the initiation of CSCs by activating Wnt/b-catenin signaling via directly binding to the promoter of DVL1, a potent activator of b-catenin. Knockdown of DVL1 significantly inhibited the transformation to stem cells in, as well as the tumorigenicity of, CRC. Activation of Wnt/b-catenin signaling by DVL1 increased pluripotent transcription factors, including c-Myc, NANOG, and SOX2. Moreover, FUBP1 was upregulated at the post-transcriptional level. Elevated FUBP1 levels in KRAS wild-type CRC patients is due to the decrease in Smurf2, which promotes ubiquitinmediated degradation of FUBP1. In contrast, FUBP1 was upregulated in KRAS-mutant patients through both inhibition of caspase 3-dependent cleavage and decreased Smurf2. Our results demonstrate, for the first time, that FUBP1 is an oncogene, initiating the development of CSCs, as well as Abbreviations ChIP, chromatin immunoprecipitation; CRC, colorectal cancer; CSCs, cancer stem cells; FUBP1, far upstream element-binding protein 1; IHC, immunohistochemistry; Real-time PCR, quantitative real-time polymerase chain reaction.

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Emerging Roles of C-Myc in Cancer Stem Cell-Related Signaling and Resistance to Cancer Chemotherapy: A Potential Therapeutic Target Against Colorectal Cancer

Cited by 201 publications

References 133 publications

Isolation and Identification of a TaTDR-Like Wheat Gene Encoding a bHLH Domain Protein, Which Negatively Regulates Chlorophyll Biosynthesis in Arabidopsis

Isolation and Identification of a TaTDR-Like Wheat Gene Encoding a bHLH Domain Protein, Which Negatively Regulates Chlorophyll Biosynthesis in Arabidopsis

Ketamine inhibits aerobic glycolysis in colorectal cancer cells by blocking the NMDA receptor‐CaMK II‐c‐Myc pathway

FUBP1 promotes colorectal cancer stemness and metastasis via DVL1‐mediated activation of Wnt/β‐catenin signaling

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