Journal of Carcinogenesis & Mutagenesis

Inflammatory Cytokines as Factors Promoting of Genetic Instability in Cancer Cells

Zhiqun Xie^* Department of Medical Biophysics, University of Toronto, Toronto, Canada
^*Correspondence: Zhiqun Xie, Department of Medical Biophysics, University of Toronto, Toronto, Canada, Email:

Received: 01-Oct-2024, Manuscript No. JCM-24-27564; Editor assigned: 03-Oct-2024, Pre QC No. JCM-24-27564 (PQ); Reviewed: 17-Oct-2024, QC No. JCM-24-27564; Revised: 24-Oct-2024, Manuscript No. JCM-24-27564 (R); Published: 31-Oct-2024, DOI: 10.35248/2157-2518.24.S46.001

Description

Genetic instability is a attribute of cancer, contributing to tumor initiation, progression and metastasis. One of the key factors driving genetic instability is inflammation, particularly through the action of inflammatory cytokines. These signaling molecules, typically produced in response to infections, injury, or tissue stress, can promote the development of cancer by inducing genetic alterations in cells. Understanding the role of inflammatory cytokines in driving genetic instability in cancer cells provides valuable insights into cancer biology and may help in the development of new therapeutic strategies [1].

Inflammatory cytokines and their role in cancer

Cytokines are small proteins that mediate communication between immune cells and regulate various aspects of the immune response, including inflammation, cell proliferation, and apoptosis. In the context of cancer, inflammatory cytokines are often produced by both immune cells and tumor cells within the tumor microenvironment. While these cytokines initially play a protective role in immune surveillance and tissue repair, chronic inflammation can lead to a cascade of events that promote cancer development [2-5].

Mechanisms of inflammatory cytokines inducing genetic instability

The production of inflammatory cytokines in the tumor microenvironment can lead to genetic instability in several ways. One key mechanism is the generation of Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS), which are by-products of the inflammatory response. ROS and RNS can cause DNA damage by inducing base modifications, strand breaks, and chromosomal aberrations. These DNA lesions can lead to mutations if not properly repaired, contributing to the genetic alterations seen in cancer cells.

For instance, TNF-α, a cytokine that plays a prominent role in inflammation, is known to stimulate the production of ROS and RNS. This can overwhelm the cell’s DNA repair machinery and promote the accumulation of genetic mutations. Over time, these mutations may drive the transformation of normal cells into cancerous ones, allowing them to bypass normal growth control mechanisms [3-6].

Additionally, inflammatory cytokines such as IL-6 can activate key signaling pathways like the JAK/STAT pathway, which has been linked to both inflammation and cancer progression. Persistent activation of these pathways can promote the expression of genes involved in cell survival, proliferation and angiogenesis, as well as genes that impair DNA repair mechanisms. This further exacerbates genetic instability in tumor cells [7].

Inflammatory cytokines and chromosomal instability

Inflammatory cytokines can also contribute to Chromosomal Instability (CIN), a type of genetic instability characterized by an increased rate of chromosomal changes such as aneuploidy and structural alterations. CIN is frequently observed in cancer cells and is associated with poor prognosis. Inflammatory cytokines like IL-1 and TNF-α have been shown to disrupt the spindle assembly checkpoint, leading to errors during cell division that result in chromosomal missegregation [8-10].

Clinical implications and therapeutic potential

The relationship between inflammatory cytokines and genetic instability highlights the potential of targeting inflammation as a therapeutic strategy in cancer treatment [10]. Anti-inflammatory therapies, such as Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) or specific inhibitors of pro-inflammatory cytokines like TNF-α or IL-6, have been investigated for their potential to reduce cancer progression by limiting the mutagenic effects of inflammation.

Conclusion

Inflammatory cytokines play a critical role in driving genetic instability in cancer cells. Through the production of reactive species and the activation of pro-survival and proliferative pathways, these cytokines contribute to the accumulation of mutations and chromosomal abnormalities that underlie cancer development. Targeting the inflammatory signaling pathways involved in genetic instability offers a potential approach for cancer treatment, with the potential to reduce tumor heterogeneity and improve patient outcomes. Understanding how inflammatory cytokines influence genetic instability in cancer provides valuable insights into the complex exchange between inflammation and tumorigenesis, prepare for novel therapeutic strategies.

References

1. Malik S, Sikander M, Wahid M, Dhasmana A, Sarwat M, Khan S, et al. Deciphering cellular and molecular mechanism of MUC13 mucin involved in cancer cell plasticity and drug resistance. Cancer Metastasis Rev. 2024;43(3):981-999.

   [Crossref] [Google Scholar] [PubMed]

2. Malik S, Sikander M, Bell N, Zubieta D, Bell MC, Yallapu MM, et al. Emerging role of mucins in antibody drug conjugates for ovarian cancer therapy. J Ovarian Res. 2024;17(1):161.

   [Crossref] [Google Scholar] [PubMed]

3. Dhasmana A, Dhasmana S, Agarwal S, Khan S, Haque S, Jaggi M, et al. Integrative big transcriptomics data analysis implicates crucial role of MUC13 in pancreatic cancer. Comput Struct Biotechnol J. 2023;21:2845-2857.

   [Crossref] [Google Scholar] [PubMed]

4. Massey AE, Doxtater K, Yallapu MM, Chauhan SC, et al. Biophysical changes caused by altered MUC13 expression in pancreatic cancer cells. Micron. 2020;130:102822.

   [Crossref] [Google Scholar] [PubMed]

5. Chauhan SC, Ebeling MC, Maher DM, Koch MD, Watanabe A, Aburatani H, et al. MUC13 mucin augments pancreatic tumorigenesis. Mol Cancer Ther. 2012;11(1):24-33.

   [Crossref] [Google Scholar] [PubMed]

6. Dai Y, Liu L, Zeng T, Liang JZ, Song Y, Chen K, et al. Overexpression of MUC13, a Poor Prognostic Predictor, Promotes Cell Growth by Activating Wnt Signaling in Hepatocellular Carcinoma. Am J Pathol. 2018;188(2):378-391.

   [Crossref] [Google Scholar] [PubMed]

7. Chauhan SC, Vannatta K, Ebeling MC, Vinayek N, Watanabe A, Pandey KK, et al. Expression and functions of transmembrane mucin MUC13 in ovarian cancer. Cancer Res. 2009;69(3):765-74.

   [Crossref] [Google Scholar] [PubMed]

8. Gupta BK, Maher DM, Ebeling MC, Stephenson PD, Puumala SE, Koch MR, et al. Functions and regulation of MUC13 mucin in colon cancer cells. J Gastroenterol. 2014;49(10):1378-91.

   [Crossref] [Google Scholar] [PubMed]

9. Kumari S, Khan S, Gupta SC, Kashyap VK, Yallapu MM, Chauhan SC, et al. MUC13 contributes to rewiring of glucose metabolism in pancreatic cancer. Oncogenesis. 2018;7(2):19.

   [Crossref] [Google Scholar] [PubMed]

10. Doxtater K. MUC13 drives cancer aggressiveness and metastasis through the YAP1-dependent pathway. Life Sci Alliance. 2023;6(12): e202301975.

    [Crossref] [Google Scholar] [PubMed]