SARS-CoV-2 Causes Cathepsin-L Upregulation Which in Turn Raises Risk of Cancer and Tumor Progression!

Thailand Medical News Exclusive: The COVID-19 pandemic caused by SARS-CoV-2 has reshaped global health, yet its implications extend beyond acute respiratory disease. Increasing evidence suggests that SARS-CoV-2 infection can influence pathways linked to cancer progression. One of the emerging connections is the upregulation of Cathepsin-L, a lysosomal cysteine protease, which plays a role in cellular processes such as protein degradation, extracellular matrix remodeling, and apoptosis. This upregulation, caused by SARS-CoV-2, can exacerbate cancer risk and progression by contributing to tumorigenesis, metastasis, and immune evasion. This Medical News article aims to educate readers about the one of the many ways that COVID-19 infections can lead to the onset of cancers or in the progression of existing cancers.


SARS-CoV-2 Causes Cathepsin-L Upregulation Which in Turn Raises Risk of Cancer
and Tumor Progression

Understanding Cathepsin-L and Its Role in Physiology
Cathepsin-L belongs to the cathepsin family of proteases, enzymes responsible for breaking down proteins. Normally, Cathepsin-L functions in lysosomal compartments to degrade cellular components. It is also involved in tissue remodeling, antigen processing, and wound healing. While its activity is necessary for normal cellular function, dysregulation of Cathepsin-L has been linked to pathological conditions, particularly cancer.
 
In cancer biology, Cathepsin-L is known for its role in promoting tumor cell invasion and metastasis. This occurs through the degradation of extracellular matrix (ECM) proteins, which allows tumor cells to break through tissue barriers and spread to distant sites. Cathepsin-L is often upregulated in several malignancies, including breast, prostate, and lung cancers, contributing to more aggressive cancer phenotypes.
 
SARS-CoV-2 and Cathepsin-L Upregulation
The entry of SARS-CoV-2 into human cells relies on specific host factors. The virus primarily uses the angiotensin-converting enzyme 2 (ACE2) receptor for attachment, but cellular proteases such as TMPRSS2 (transmembrane serine protease 2) and Cathepsin-L facilitate viral entry by priming the spike (S) protein. Cathepsin-L specifically plays a role in endosomal processing of the virus, enabling it to fuse with host cell membranes and deliver its genetic material.
 
During SARS-CoV-2 infection, evidence suggests that Cathepsin-L expression is upregulated as a host response to increased viral load. This upregulation serves to assist viral entry and replication. However, persistent Cathepsin-L elevation creates a pathological environment conducive to cancer initiation and progression. Elevated levels of Cathepsin-L can damage cellular structures, trigger inflammation, and promote tissue remodeling, all of which are hallmarks of carcinogenesis.
 
Mechanisms Linking Cathepsin-L to Cancer Progression
-Degradation of the Extracellular Matrix
One of the key roles of Cathepsin-L in cancer progression is the degradation of ECM proteins such as collagen and elastin. This process weakens tissue barriers, facilitating tumor cell invasion and metastasis. SARS-CoV-2-induced Cathepsin-L upregulation amplifies this process, thereby accelerating the metastatic potential of existing tumors or increasing susceptibility to cancer formation.
 
-Increased Inflammatory Response
SARS-CoV-2 infection is associated with a hyperinflammatory state, often referred to as a cytokine storm. Inflammation is a well-recognized contributor to cancer development, as it promotes DNA damage, oxidative stress, and angiogenesis. Cathepsin-L contributes to this inflammatory environment by activating key signaling pathways, such as nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs), both of which are associated with cell proliferation and survival.
 
-Immune Evasion
Cancer cells often evade immune surveillance through multiple mechanisms, one of which involves proteolytic enzymes like Cathepsin-L. Elevated levels of Cathepsin-L impair the ability of immune cells to detect and destroy tumor cells by degrading antigens and modulating antigen presentation pathways. In SARS-CoV-2 infections, Cathepsin-L upregulation may further suppress immune responses, creating an environment that supports tumor immune evasion.
 
-Promotion of Tumor Cell Proliferation
Studies have shown that Cathepsin-L can activate signaling cascades such as the PI3K/Akt and MAPK pathways, which promote cell proliferation and survival. SARS-CoV-2-mediated upregulation of Cathepsin-L may therefore exacerbate uncontrolled cell division, increasing cancer progression risk, particularly in individuals with pre-existing conditions or genetic predispositions.
 
Evidence From Clinical and Experimental Studies
Clinical and laboratory studies are beginning to uncover the link between SARS-CoV-2 and cancer progression through Cathepsin-L. In vitro studies have demonstrated that SARS-CoV-2 infection significantly increases Cathepsin-L expression in infected cells. Additionally, patients with severe COVID-19 often exhibit higher Cathepsin-L levels in their serum, suggesting a systemic effect of the virus.
 
Research on cancer patients who contracted COVID-19 further supports these findings. Cancer patients infected with SARS-CoV-2 experience poorer outcomes, with increased rates of metastasis and disease progression. The upregulation of Cathepsin-L in these patients likely plays a role in exacerbating cancer-related processes.
 
Animal models have also demonstrated that Cathepsin-L inhibition can reduce tumor growth and metastasis, further underscoring its role in cancer progression. This evidence highlights the need to explore Cathepsin-L as a potential therapeutic target in SARS-CoV-2-infected individuals.
 
Implications for Cancer Patients During the COVID-19 Pandemic
The intersection of COVID-19 and cancer has created new challenges for healthcare providers. Cancer patients are already immunocompromised and vulnerable to infections, and SARS-CoV-2 infection may further accelerate their disease progression. The upregulation of Cathepsin-L adds an additional layer of complexity, as it not only facilitates viral entry but also promotes tumor progression.
 
For oncologists and researchers, this evidence underscores the importance of monitoring Cathepsin-L levels in COVID-19 patients, particularly those with pre-existing malignancies. Targeted therapies aimed at inhibiting Cathepsin-L activity could offer a dual benefit: reducing SARS-CoV-2 infectivity and mitigating cancer progression.
 
Potential Therapeutic Strategies
-Cathepsin-L Inhibitors
Several pharmacological inhibitors of Cathepsin-L are currently under investigation for their potential role in cancer therapy. Drugs such as E64 and K11777 have shown promise in preclinical studies by reducing Cathepsin-L activity and suppressing tumor growth. Repurposing these inhibitors for COVID-19 patients could help reduce the impact of viral infection on cancer progression.
 
-Anti-Inflammatory Therapies
Since inflammation is a common denominator in both COVID-19 and cancer, anti-inflammatory drugs such as corticosteroids or cytokine inhibitors may help mitigate the harmful effects of Cathepsin-L upregulation. These therapies could reduce inflammation-driven cancer progression while improving COVID-19 outcomes.
 
Conclusion
SARS-CoV-2 infection presents an unexpected risk factor for cancer progression, largely due to its ability to upregulate Cathepsin-L. This protease, while critical for viral entry, also plays a central role in cancer metastasis, inflammation, and immune evasion. Understanding this connection provides an opportunity to develop novel therapeutic strategies that target Cathepsin-L, offering hope for improved outcomes in cancer patients during the ongoing pandemic. Future research is essential to fully unravel the mechanisms underlying SARS-CoV-2-driven Cathepsin-L upregulation and its long-term implications for cancer biology.
 
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Read Also:
https://www.thailandmedical.news/news/researchers-warn-that-covid-19-may-contribute-to-the-development-of-thyroid-cancer
 
https://www.thailandmedical.news/news/covid-19-worsens-existing-liver-disease-and-could-spur-liver-cancer-development
 
https://www.thailandmedical.news/articles/coronavirus
 
https://www.thailandmedical.news/articles/cancer
 
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