Transcriptional reactivation of TERT, the catalytic subunit of telomerase, is necessary for cancer progression in about 90% of human cancers. The recent discovery of two prevalent somatic mutations—C250T and C228T—in the TERT promoter in various cancers has provided insight into a plausible mechanism of TERT reactivation. Although the two hotspot mutations create a similar binding motif for E-twenty-six (ETS) transcription factors, we show that they are functionally distinct, in that the C250T unlike the C228T TERT promoter is driven by non-canonical NF-κB signalling. We demonstrate that binding of ETS to the mutant TERT promoter is insufficient in driving its transcription but this process requires non-canonical NF-κB signalling for stimulus responsiveness, sustained telomerase activity and hence cancer progression. Our findings highlight a previously unrecognized role of non-canonical NF-κB signalling in tumorigenesis and elucidate a fundamental mechanism for TERT reactivation in cancers, which if targeted could have immense therapeutic implications.

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The outbreak of the new Coronavirus disease, COVID-19, has been involved in 77,262 cases in China as well as in 27 other countries as of February 24, 2020. Because the virus is novel to human beings, and there is no vaccine yet available, every individual is susceptible and can become infected. Healthcare workers are at high risk, and unfortunately, more than 3,000 healthcare workers in China have been infected. Anesthesiologists are among healthcare workers who are at an even higher risk of becoming infected because of their close contact with infected patients and high potential of exposure to respiratory droplets or aerosol from their patients’ airways. In order to provide healthcare workers with updated recommendations on the management of patients in the perioperative setting as well as for emergency airway management outside of the operating room, the two largest anesthesia societies, the Chinese Society of Anesthesiology (CSA) and the Chinese Association of Anesthesiologists (CAA) have formed a task force to produce the recommendations. The task force hopes to help healthcare workers, particularly anesthesiologists, optimize the care of their patients and protect patients, healthcare workers, and the public from becoming infected. The recommendations were created mainly based on the practice and experience of anesthesiologists who provide care to patients in China. Therefore, adoption of these recommendations outside of China must be done with caution, and the local environment, culture, uniqueness of the healthcare system, and patients’ needs should be considered. The task force will continuously update the recommendations and incorporate new information in future versions.