Metabolic Pathways Regulating Colorectal Cancer: A Potential Therapeutic
Approach

Zafari, Nima; Velayati, Mahla; Damavandi, Sedigheh; Avan, Amir; Pourali, Ghazale; Mobarhan, Majid Ghayour; Nassiri, Mohammadreza; Hassanian, Seyed Mahdi; Khazaei, Majid; Ferns, Gordon A.

doi:10.2174/1381612828666220922111342

Cited by 12 publications

(4 citation statements)

References 172 publications

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“…Specifically, cancer cells primarily absorb energy dependent on a metabolic phenotype known as aerobic glycolysis that is also recognized as a phenomenon termed the Warburg effect, where cancer cells preferentially convert glucose to lactate ( 31 ). It is widely accepted that aerobic glycolysis plays a critical role in promoting the tumorigenesis of CRC ( 32 , 33 ). As an essential enzyme in the process of glycolysis, ENO1 has been hypothesized to exert pivotal functions in aerobic glycolysis in a variety of tumors, such as lung adenocarcinoma ( 34 ), pancreatic cancer ( 35 ) and gastric cancer ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

ENO1 deletion potentiates ferroptosis and decreases glycolysis in colorectal cancer cells via AKT/STAT3 signaling

Liu,

Hou,

Zhang

et al. 2024

Exp Ther Med

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Colorectal cancer (CRC) is one of the most prevailing and lethal forms of cancer globally. α-enolase (ENO1) has been well documented to be involved in the progression and drug resistance of CRC. The present study was designed to specify the role of ENO1 in major events during the process of CRC and to introduce its latent functional mechanism. ENO1 expression was determined by western blot analysis. Extracellular acidification rates were assessed using an XF96 extracellular flux analyzer. Glucose uptake, lactic acid production, total iron levels and ferroptosis-related markers were examined with corresponding kits. A dichlorodihydrofluorescein diacetate probe measured intracellular reactive oxygen species content. Western blotting detected the expression of glycolysis- and ferroptosis-related proteins. CCK-8 and EdU staining assays assessed cell proliferation. In the current study, ENO1 was highly expressed in CRC cells. Knockdown of ENO1 markedly reduced the glycolysis and accelerated the ferroptosis in CRC cells. Moreover, the inhibitory effects of WZB117, a specific inhibitor of glycolysis-related glucose transporter type 1, on CRC cell proliferation were further enhanced by ENO1 interference. In addition, silencing of ENO1 inactivated the AKT/STAT3 signaling. The AKT activator SC79 partially reversed the effects of ENO1 deficiency on the AKT/STAT3 signaling, glycolysis, proliferation as well as ferroptosis in CRC cells. In summary, inactivation of AKT/STAT3 signaling mediated by ENO1 inhibition might boost the ferroptosis and suppress the glycolysis in CRC cells.

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Section: Discussionmentioning

confidence: 99%

ENO1 deletion potentiates ferroptosis and decreases glycolysis in colorectal cancer cells via AKT/STAT3 signaling

Liu,

Hou,

Zhang

et al. 2024

Exp Ther Med

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“…Based on data from TCGA, the present study revealed that the expression of TNS4 was significantly associated with glycolysis-related genes (namely, HK2, LDHB, LDHM, PKM and SLC2A1) in the CRC tissue samples, suggesting that TNS4 may be involved in the regulation of aerobic glycolysis in CRC. Aerobic glycolysis, as a key hallmark of cancer, has been demonstrated to be associated with tumor growth, metastasis and drug resistance in CRC (33,34). Shi et al (21) reported that B7 homolog 3, an immunoregulatory protein, enhanced the chemoresistance of CRC cells by promoting HK2-mediated aerobic glycolysis.…”

Section: Discussionmentioning

confidence: 99%

Tensin 4 facilitates aerobic glycolysis, migration and invasion of colorectal cancer cells through the β‑catenin/c‑Myc signaling pathway

Wang,

Lu,

2024

Oncol Lett

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Tensin 4 (TNS4) is overexpressed in multiple cancers, including colorectal cancer (CRC), and is associated with a poor prognosis of patients with CRC. However, the role and underlying mechanisms of TNS4 in CRC have yet to be elucidated. The expression of TNS4 in CRC tissues were analyzed by immunohistochemistry. Cell migration and invasion were assessed in vitro using Transwell assay. Western blot and reverse transcription (RT)-quantitative (q)PCR were used to investigate the molecular mechanisms by which TNS4 regulates aerobic glycolysis, migration and invasion of CRC cells. The present study demonstrated that TNS4 was highly expressed in the cancer tissues of patients with CRC and significantly associated with the tumor-node-metastasis stages. TNS4 silencing led to a significant decrease in glucose consumption and lactate production in CRC cells, and knockdown of TNS4 suppressed the migration and invasion of CRC cells via aerobic glycolysis through the β-catenin/c-Myc pathway. Notably, treatment with DASA-58, an activator of glycolysis, or SKL2001, an activator of β-catenin/c-Myc signaling, significantly reversed the effect of TNS4 knockdown on aerobic glycolysis, migration and invasion of CRC cells. Collectively, these results suggest that TNS4 may act as a novel regulator of aerobic glycolysis, migration and invasion of CRC cells by modulating β-catenin/c-Myc signaling, providing a new potential biomarker and therapeutic target in CRC.

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“…These findings suggest that the gut microbiota could serve as a potential biomarker for NAT response and prognosis in PDAC patients and warrant further investigation [106]. Cancer metabolic phenotypes have been extensively investigated by metabolic analyses, allowing for the identification of diagnostic and prognostic biomarkers to improve therapeutic management [107,108]. ).…”

Section: Microbiome As Prognostic Biomarker In Pcmentioning

confidence: 99%

Microbiome as a biomarker and therapeutic target in pancreatic cancer

Pourali,

Kazemi,

Chadeganipour

et al. 2024

BMC Microbiol

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Studying the effects of the microbiome on the development of different types of cancer has recently received increasing research attention. In this context, the microbial content of organs of the gastrointestinal tract has been proposed to play a potential role in the development of pancreatic cancer (PC). Proposed mechanisms for the pathogenesis of PC include persistent inflammation caused by microbiota leading to an impairment of antitumor immune surveillance and altered cellular processes in the tumor microenvironment. The limited available diagnostic markers that can currently be used for screening suggest the importance of microbial composition as a non-invasive biomarker that can be used in clinical settings. Samples including saliva, stool, and blood can be analyzed by 16 s rRNA sequencing to determine the relative abundance of specific bacteria. Studies have shown the potentially beneficial effects of prebiotics, probiotics, antibiotics, fecal microbial transplantation, and bacteriophage therapy in altering microbial diversity, and subsequently improving treatment outcomes. In this review, we summarize the potential impact of the microbiome in the pathogenesis of PC, and the role these microorganisms might play as biomarkers in the diagnosis and determining the prognosis of patients. We also discuss novel treatment methods being used to minimize or prevent the progression of dysbiosis by modulating the microbial composition. Emerging evidence is supportive of applying these findings to improve current therapeutic strategies employed in the treatment of PC.

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Metabolic Pathways Regulating Colorectal Cancer: A Potential Therapeutic Approach

Cited by 12 publications

References 172 publications

ENO1 deletion potentiates ferroptosis and decreases glycolysis in colorectal cancer cells via AKT/STAT3 signaling

ENO1 deletion potentiates ferroptosis and decreases glycolysis in colorectal cancer cells via AKT/STAT3 signaling

Tensin 4 facilitates aerobic glycolysis, migration and invasion of colorectal cancer cells through the β‑catenin/c‑Myc signaling pathway

Microbiome as a biomarker and therapeutic target in pancreatic cancer

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