Cell & Developmental Biology
Open Access

Impact of CDC7 Inhibition:Inflammatory Response and p53-Dependent Senescent-Like State in Breast Epithelial Cells

Zainul Gree Tran^{* *}Correspondence: Zainul Gree Tran, Department of Cellular Biophysics, Max Planck Institute for Medical Research, Heidelberg, Germany, Email:

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Description

Breast cancer is a prevalent malignancy affecting millions of individuals worldwide. Understanding the molecular mechanisms underlying its progression is potential for developing effective therapeutic strategies. Recent research has illuminate on the role of Cell Division Cycle 7 (CDC7), a serine/threonine kinase critical for DNA replication initiation, in breast epithelial cell biology. Inhibition of CDC7 has been identified as a potential therapeutic avenue, but its effects on cellular behavior, particularly inflammation and senescence, remain less explored.

Key aspects and functions of CDC7

Initiation of DNA replication: CDC7 kinase activity is required for the initiation of DNA replication at origins of replication. It phosphorylates the Mini Chromosome Maintenance (MCM) complex, a key component of the pre-Replication Complex (pre- RC), to facilitate its activation and helicase loading onto DNA, allowing the replication fork to form and progress.

Cell cycle regulation: CDC7 activity is thoroughly regulated throughout the cell cycle to ensure proper timing and coordination of DNA replication with other cellular processes. Its activity peaks during the G1/S phase transition, coinciding with the initiation of DNA replication, and declines as cells progress through S phase and enter mitosis.

Maintenance of genome stability: By ensuring accurate and timely DNA replication, CDC7 plays a critical role in maintaining genome stability. Dysregulation of CDC7 activity can lead to genomic instability, a feature of cancer, by causing defects in DNA replication and DNA damage response pathways.

Therapeutic target in cancer: Given its essential role in DNA replication and cell cycle control, CDC7 has emerged as a good target for cancer therapy. Inhibitors of CDC7 kinase activity have shown potential as anti-cancer agents by selectively targeting rapidly dividing cancer cells while sparing normal cells.

Therapeutic implications: Targeting CDC7 kinase presents a potential therapeutic strategy for inflammation-related diseases. Preclinical studies utilizing CDC7 inhibitors have shown efficacy in attenuating inflammation in models of autoimmune diseases and inflammatory disorders.

Genomic instability and inflammation: CDC7 inhibitioninduced replication stress can trigger DNA damage and genomic instability, leading to the activation of inflammatory signaling pathways. Understanding the interaction between CDC7 inhibition, DNA damage, and inflammation is important for elucidating disease mechanisms and developing targeted therapies.

Mechanisms of inflammatory response: The study elucidates the mechanisms underlying the inflammatory response triggered by CDC7 inhibition. It reveals the activation of key inflammatory mediators, such as Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Signal Transducer and Activator of Transcription 3 (STAT3), upon CDC7 suppression. These signaling pathways play pivotal roles in regulating immune responses and are frequently dysregulated in cancer. The activation of NF-κB and STAT3 emphasize the interaction between cell cycle regulation and inflammation in breast epithelial cells.

Implications for breast cancer therapy

The identification of CDC7 inhibition as a modulator of inflammation in breast epithelial cells holds significant therapeutic implications. Targeting inflammatory pathways along with conventional anticancer strategies could enhance treatment efficacy and reduce tumor-promoting inflammation. Moreover, understanding the relation between CDC7 and inflammatory signaling pathways may facilitate the development of novel targeted therapies for breast cancer.

CDC7 inhibition and senescence

In addition to driving inflammation, CDC7 inhibition induces a p53-dependent senescent-like state in breast epithelial cells. Senescence is a cellular state characterized by irreversible growth inhibition, often triggered in response to various stressors, including DNA damage. The study highlights the involvement of p53, a key tumor suppressor protein, in mediating the senescence response following CDC7 inhibition.

Implications for cancer therapy

Senescence induction represents a paradoxical situation in cancer therapy. On one hand, senescence can suppress tumor growth by delaying the proliferation of malignant cells. On the other hand, senescent cells can contribute to tumor progression through the secretion of pro-inflammatory factors and remodeling of the tumor microenvironment. Understanding the contextdependent effects of senescence induction is important for optimizing therapeutic strategies targeting CDC7 in breast cancer.

Conclusion

The study indicates the multifaceted impact of CDC7 inhibition on breast epithelial cell behavior, encompassing both inflammatory response activation and the induction of a p53- dependent senescent-like state. These findings not only broaden our understanding of CDC7 function but also provide valuable insights into the complex interaction between cell cycle regulation, inflammation, and senescence in breast cancer pathogenesis. Future research aimed at elucidating the molecular mechanisms underlying these processes may involve in the development of innovative therapeutic approaches for breast cancer patients.