A potential new therapeutic approach to cancer
Links between biological clock proteins, inflammation and cell metabolism may open new avenues for developing cancer therapy.
doi:10.1038/nindia.2021.125 Published online 30 September 2021
A study has provided new insights into the molecular mechanisms that aid the proliferation of cancer cells, particularly those that affect the central nervous system (CNS)1.
The human biological clock or circadian rhythm controls the proliferation of normal cells. Cancer cells, however, escape this rhythm to sustain uncontrolled growth.
Cancer cells reprogram their metabolism and utilise lactate dehydrogenase (LDHA), an enzyme that converts pyruvate to lactate. Lactate is known to fuel tumour growth.
The scientists, from the National Brain Research Centre in Haryana, India, found that the cancer cells could modify the molecular components of cellular circadian rhythm to create a new regulatory network. This network produces more lactate and IL-1β, a small immune protein with roles in cancer development and progression. Such a feed-forward network is the Lactate-Inflammation-Clock (LIC).
The team, led by Ellora Sen, used chemicals to activate or inhibit lactate and IL-1β in glioma cells, a type of tumor that occurs in the CNS. They found that, when activated, lactate and IL-1β induce the expression of important circadian proteins called Clock and Bmal1.
Such interaction is present in stomach and cervical cancer cells, the researchers note. Computer-based analysis showed that patients with stomach, cervical and brain cancers survived longer when they had lower levels of Clock, Bmal1, LDHA and IL-1β protein.
The researchers say that the findings could serve as a framework for a new therapeutic approach to cancer.
1. Gowda, P. et al. Mol. Cell. Biol.41, e0044920 (2021) Doi: 10.1128/mcb.00449-20