Cancer cell proliferation
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Cancer Cell Proliferation: Key Mechanisms and Regulatory Pathways
Uncontrolled Cell Proliferation as a Hallmark of Cancer
Uncontrolled cell proliferation is a defining feature of cancer. Tumor cells often acquire genetic changes that disrupt normal cell cycle regulation, leading to unchecked growth and division. Key regulators of the cell cycle, such as p16INK4a, cyclin D1, and the retinoblastoma protein (RB), are frequently altered in human cancers, making the inactivation of these pathways almost necessary for tumor development 749. This deregulation is often accompanied by the suppression of apoptosis, allowing cancer cells to survive and expand .
Cell Cycle Deregulation and Cancer Progression
The cell cycle machinery acts as a central integration point for signals that control cell growth. Mutations that hyperactivate growth signaling pathways, combined with the loss of tumor suppressor functions, drive the oncogenic proliferation seen in cancer 97. Some tumor cells display "cell cycle coherence," where cell cycle regulators are expressed in expected patterns, while others show non-canonical or skewed expression, which is linked to more aggressive tumor behavior . These patterns can vary within different regions of a tumor and change in response to oncogene activity or therapy .
Metabolic Reprogramming Fuels Proliferation
Cancer cells reprogram their metabolism to support rapid growth and division. They often shift from oxidative phosphorylation to aerobic glycolysis (the Warburg effect), increase glutaminolysis, and alter pathways like the pentose phosphate pathway and lipid biosynthesis to meet the demands for energy and building blocks 310. These metabolic changes are regulated by oncogenes and tumor suppressors, such as the PI3K/Akt/mTOR pathway, HIF-1, and Myc 310. The metabolic plasticity of cancer cells allows them to adapt to different environments and supports sustained proliferation .
The Role of Cell Proliferation in Carcinogenesis
Increased cell proliferation is not only a feature of cancer but also plays a role in the development of tumors, especially in response to certain chemicals. Both genotoxic and nongenotoxic agents can promote cancer by increasing cell proliferation in target tissues . However, while cell proliferation is critical for cancer development, it is still debated whether proliferation alone, without other factors, is a direct risk factor for cancer . There is no clear evidence that cell proliferation by itself, in the absence of carcinogenic exposure, leads to cancer .
Therapeutic Implications and Targets
Targeting the cell cycle and its regulatory pathways is a promising strategy for cancer therapy. Analysis of cell cycle proteins and DNA replication machinery is leading to the identification of new biomarkers and therapeutic targets . However, not all cell cycle regulators are equally important in all cancers. For example, inhibition of CDK2 does not always stop cancer cell proliferation, suggesting that some targets may not be universally effective . Natural compounds and drugs that inhibit key signaling pathways involved in proliferation, such as PI3K/Akt, HIF-1, and hormone receptors, are being explored for their potential to block tumor growth .
Conclusion
Cancer cell proliferation is driven by complex interactions between genetic mutations, deregulated cell cycle control, and metabolic reprogramming. While increased proliferation is central to cancer development and progression, it is not always sufficient on its own to cause cancer. Understanding the diverse mechanisms that support sustained proliferation in cancer cells is crucial for developing effective diagnostic tools and targeted therapies 13467910.
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