ChemDiv follows trends in biology and chemistry to supply clients with high scientific and up-to-date service. We will share reviews on Nature and Science Journal articles that we found the most interesting this month. Here is the first part of the June reviews. Today we observe oncology, immunology, drug research, and genetic engineering.
Correia, A.L., Guimaraes, J.C., Auf der Maur, P. et al. Hepatic stellate cells suppress NK cell-sustained breast cancer dormancy. Nature 594, 566–571 (2021)
The persistence of dormant tumor cells after primary tumor removal poses a major challenge to effective cancer treatment. These dormant cells are seeds of future metastases. In their new study, scientists show that different tissue-specific microenvironments restrain or allow the progression of cancer in the liver—a frequent site of metastasis. Natural killer (NK) cells sustain dormancy of tumor cells through interferon-γ signaling, thereby preventing hepatic metastases and prolonging survival. Exit from dormancy is a result of the contraction of the NK cell compartment and the concurrent accumulation of hepatic stellate cells. In this way, the interaction between these cell lines is a switch of cancer dormancy. Therefore, therapies aimed at normalizing the NK cell pool might succeed in preventing metastatic outgrowth.
Yum, M.K., Han, S., Fink, J. et al. Tracing oncogene-driven remodelling of the intestinal stem cell niche. Nature 594, 442–447 (2021).
In fact, the tumor microenvironment constitutes a complex ecosystem that comprises mutant and wild-type cells, as well as endothelial, immune, and mesenchymal cells. It is not surprising that interactions between tumor cells and the surrounding microenvironment contribute to tumor progression, metastasis, and recurrence. This was shown on the example of oncogene-expressing mutant crypts (narrow but deep invaginations in the small intestine). These mutant crypts alter the cellular organization of neighboring wild-type crypts, promoting field transformation dominated by oncogenic clones.
Yousefzadeh, M.J., Flores, R.R., Zhu, Y. et al. An aged immune system drives senescence and ageing of solid organs. Nature 594, 100–105 (2021).
Ageing of the immune system contributes to the morbidity and mortality of the elderly. To define the contribution of the immune system ageing to organism ageing, scientists selectively deleted the gene Ercc1in mouse hematopoietic cells, which encodes a crucial DNA repair protein, to increase senescence in the immune system only. Notably, non-lymphoid organs also showed increased senescence and damage, which suggests that senescent, aged immune cells can promote systemic ageing.
Braga, L., Ali, H., Secco, I. et al. Drugs that inhibit TMEM16 proteins block SARS-CoV-2 spike-induced syncytia. Nature 594, 88–93 (2021).
COVID-19 is a disease with unique characteristics. In their new study, scientists show that the lungs of patients with COVID-19 contain infected pneumocytes with abnormal morphology and frequent multinucleation. The generation of these syncytia results from activation of the SARS-CoV-2 spike protein. The authors of this research performed screening with more than 3,000 approved drugs to search for inhibitors of spike-driven syncytia. One of the most effective molecules was the anthelminthic drug nicodamid, which suppressed the activity of protein TMEM16F.
Delilah Jewel, Abhishek Chatterjee. Rewriting the genetic code. Science 372, 1040-1041 (2021).
The genetic code governs the synthesis of proteins in all domains of life using just 20 amino acid building blocks out of 500 found in nature. Progress has been made toward artificially expanding the genetic code to enable the incorporation of noncanonical amino acids (ncAAs) into proteins in living cells. Actually, it enables powerful new ways to probe and manipulate protein functions. However, this approach has been largely restricted to the incorporation of a single ncAA into a polypeptide. In a new article, researchers report the site-specific incorporation of multiple distinct ncAAs into proteins. The ability to generate designer proteins will unlock the development of new classes of biotherapeutics and biomaterials with innovative properties.