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INTERNATIONAL CONGRESS OF

CancerGenetics

• The Dual Role of LOX Proteins in Cancer: Drivers of Progression and Suppression

• Mohsen Eghtedari,¹ Fatemeh Soleimanian,^2,* sara aliakbari,³
  1. Amol university of special modern technologies,
  2. Islamic Azad University، Science And Research Branch
  3. islamic azad university
  
  
  
• Introduction: Cancer is a complex disease driven by uncontrolled cell growth and the formation of malignant tumors. Lipid metabolism plays a significant role in cancer initiation and progression, with metabolic disorders such as obesity, insulin resistance, and chronic inflammation linked to increased cancer risk. Reactive oxygen species (ROS), highly reactive molecules, contribute to carcinogenesis by damaging lipids, proteins, and DNA. Elevated ROS levels are often triggered by the binding of oxidized low-density lipoprotein (ox-LDL) to the LOX-1 receptor. While the role of ROS is clear, the involvement of lysyl oxidase (LOX) proteins in cancer progression remains more complex. This study examines how LOX proteins influence lipid metabolism and tumor behavior, exploring their dual function as both cancer promoters and suppressors, depending on the tumor environment and cancer type.
• Methods: The research involved a review of studies that assessed LOX expression and function across various cancer types, including breast, colorectal, pancreatic, hepatocellular carcinoma (HCC), prostate, and lung cancers. Techniques such as gene expression profiling and RNA silencing were used to investigate LOX's effects on cancer cell proliferation, migration, invasion, and angiogenesis. A key area of focus was LOX’s role in remodeling the extracellular matrix (ECM), the network of proteins that supports cell structure. LOX proteins increase ECM stiffness by cross-linking collagen and elastin, which enhances the invasive ability of cancer cells. The study also investigated LOX’s involvement in promoting epithelial-mesenchymal transition (EMT), a process through which cancer cells gain more aggressive traits, becoming more migratory and invasive.
• Results: LOX proteins, particularly LOX-1, were frequently upregulated in various cancers, driving tumor growth and metastasis. In breast cancer, higher LOX expression was linked to larger tumors, more advanced stages, and poor prognosis, especially in hormone receptor-negative cases. LOX silencing in breast cancer cells reduced their ability to migrate and invade, likely due to the downregulation of matrix metalloproteinases (MMP-2 and MMP-9), which facilitate ECM degradation. In hepatocellular carcinoma (HCC), LOX expression correlated with worse patient outcomes, early recurrence, and increased EMT activity. Silencing LOX in HCC cells reduced tumor proliferation and migration, as well as the production of vascular endothelial growth factor (VEGF), a critical factor in angiogenesis. Other cancers also showed significant roles for LOX. In gastric cancer, high LOX expression was associated with greater lymph node metastasis and poor patient outcomes. In non-small cell lung cancer (NSCLC), LOXL2 was upregulated in advanced disease stages, with microRNAs targeting LOXL2 found to suppress lung cancer cell growth and invasiveness. Although LOX commonly promotes cancer, in certain contexts it acts as a tumor suppressor. In prostate cancer, LOX showed a paradoxical role, sometimes promoting metastasis but also suppressing tumor growth in other cases. A similar pattern was observed in colorectal cancer, where LOX’s role varied depending on whether it was located inside or outside the cell, indicating the importance of cellular context. This duality in LOX’s behavior suggests its role in cancer progression is not uniform across all cancer types. While LOX typically drives metastasis, in specific cancers like prostate and colorectal, it may inhibit tumor progression. This complexity highlights the need for further research to better understand how LOX’s actions are influenced by its tumor microenvironment.
• Conclusion: LOX proteins play a crucial but complex role in cancer, acting as both promoters and suppressors of tumor growth. In many cancers, LOX proteins contribute to metastasis by stiffening the ECM, allowing cancer cells to invade new areas. However, in certain conditions, LOX can also suppress tumor growth, making it a complicated target for cancer therapy. Targeting LOX presents opportunities but also challenges for cancer treatment. Inhibiting LOX could help reduce metastasis and improve outcomes in cancers like breast and hepatocellular carcinoma. However, because LOX also has tumor-suppressing functions in some cancers, therapies need to be tailored carefully to avoid negative effects. Understanding the mechanisms that dictate LOX’s role in different cancers is crucial for developing effective therapies. In summary, LOX proteins represent a promising yet complex target in cancer therapy. Their ability to both promote and inhibit cancer progression, depending on the tumor environment, suggests that future treatments could focus on either inhibiting or enhancing LOX activity to achieve the desired outcomes in various cancers.
• Keywords: Cancer ,LOX (Lysyl Oxidase),Epithelial-Mesenchymal Transition (EMT),Extracellular Matrix (ECM),React