Wingless/It/β-catenin signaling in liver metastasis from colorectal cancer: A focus on biological mechanisms and therapeutic opportunities

Selvaggi, Federico; Catalano, Teresa; Lattanzio, Rossano; Cotellese, Roberto; Aceto, Gitana María

doi:10.3748/wjg.v29.i18.2764

Cited by 4 publications

(1 citation statement)

References 146 publications

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“…Molecular dysregulation of the Wnt pathway is strongly associated with the hepatic microenvironment and may drive the progression from precancerous dysplasia to PLC metastasis [26,[39][40][41]. This is a common condition also reported in liver metastasis from colorectal cancer [42].…”

Section: Introductionmentioning

confidence: 96%

Infectious Agents Induce Wnt/β-Catenin Pathway Deregulation in Primary Liver Cancers

et al. 2023

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Interaction between infectious agents and liver tissue, as well as repeated and extreme biological events beyond adaptive capacities, may result in pathological conditions predisposing people to development of primary liver cancers (PLCs). In adults, PLCs mainly comprise hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Various infectious agents in the hepatic microenvironment can destabilize normal liver cell functions by modulating the Wnt/β-catenin pathway components. Among them, hepatotropic viruses B, C, and D are involved in Wnt/β-catenin signaling dysregulation. Other microbial agents, including oncogenic viruses such as Epstein–Barr virus (EBV) and human papilloma virus (HPV), bacteria, e.g., Mycoplasma hyorhinis and Salmonella Typhi, the protozoan parasite Toxoplasma gondii, the fungus Aspergillus flavus, and liver flukes such as Clonorchissinensis or Opisthorchis viverrini, may induce malignant transformation in hepatocytes or in target cells of the biliary tract through aberrant Wnt signaling activation. This review focuses on new insights into infectious agents implicated in the deregulation of Wnt signaling and PLC development. Since the Wnt/β-catenin pathway is a driver of cancer following viral and bacterial infections, molecules inhibiting the complex axis of Wnt signaling could represent novel therapeutic approaches in PLC treatment.

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Section: Introductionmentioning

confidence: 96%

Infectious Agents Induce Wnt/β-Catenin Pathway Deregulation in Primary Liver Cancers

et al. 2023

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Differential Regulation of Wingless-Wnt/c-Jun N-Terminal Kinase Crosstalk via Oxidative Eustress in Primary and Metastatic Colorectal Cancer Cells

Aceto,

Pagotto,

Del Pizzo

et al. 2024

Biomedicines

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In the tumor microenvironment (TME), ROS production affects survival, progression, and therapy resistance in colorectal cancer (CRC). H2O2-mediated oxidative stress can modulate Wnt/β-catenin signaling and metabolic reprogramming of the TME. Currently, it is unclear how mild/moderate oxidative stress (eustress) modulates Wnt/β-catenin/APC and JNK signaling relationships in primary and metastatic CRC cells. In this study, we determined the effects of the H2O2 concentration inducing eustress on isogenic SW480 and SW620 cells, also in combination with JNK inhibition. We assessed cell viability, mitochondrial respiration, glycolysis, and Wnt/β-catenin/APC/JNK gene and protein expression. Primary CRC cells were more sensitive to H2O2 eustress combined with JNK inhibition, showing a reduction in viability compared to metastatic cells. JNK inhibition under eustress reduced both glycolytic and respiratory capacity in SW620 cells, indicating a greater capacity to adapt to TME. In primary CRC cells, H2O2 alone significantly increased APC, LEF1, LRP6, cMYC and IL8 gene expression, whereas in metastatic CRC cells, this effect occurred after JNK inhibition. In metastatic but not in primary tumor cells, eustress and inhibition of JNK reduced APC, β-catenin, and pJNK protein. The results showed differential cross-regulation of Wnt/JNK in primary and metastatic tumor cells under environmental eustress conditions. Further studies would be useful to validate these findings and explore their therapeutic potential.

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Recommendations for articles and reviews in colorectal cancer-related research at the year-end of 2023

Luan,

Lin,

Miao

2024

World J Gastroenterol

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As peer reviewers of the World Journal of Gastroenterology , our weekly routine involves immersing ourselves in the newly published issue, particularly focusing on the realm of colorectal cancer (CRC) research. We diligently sift through various contributions, ranging from comprehensive reviews to original articles and other scholarly works. Through meticulous examination, we discern the most notable papers, delving into each with careful scrutiny to distill their merits and shortcomings. Undoubtedly, this undertaking demands considerable time and effort. Yet, it stands as an indispensable pursuit, affording us a profound comprehension of the latest breakthroughs in CRC research. Moreover, these meticulously curated selections furnish readers with invaluable resources, serving as enduring references for the nuanced exploration of this dynamic field.

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Wingless/It/β-catenin signaling in liver metastasis from colorectal cancer: A focus on biological mechanisms and therapeutic opportunities

Cited by 4 publications

References 146 publications

Infectious Agents Induce Wnt/β-Catenin Pathway Deregulation in Primary Liver Cancers

Infectious Agents Induce Wnt/β-Catenin Pathway Deregulation in Primary Liver Cancers

Differential Regulation of Wingless-Wnt/c-Jun N-Terminal Kinase Crosstalk via Oxidative Eustress in Primary and Metastatic Colorectal Cancer Cells

Recommendations for articles and reviews in colorectal cancer-related research at the year-end of 2023

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