Recent work in several model organisms has revealed that apoptotic cells are able to stimulate neighboring surviving cells to undergo additional proliferation, a phenomenon termed apoptosis-induced proliferation. This process depends critically on apoptotic caspases such as Dronc, the Caspase-9 ortholog in Drosophila, and may have important implications for tumorigenesis. While it is known that Dronc can induce the activity of Jun N-terminal kinase (JNK) for apoptosis-induced proliferation, the mechanistic details of this activation are largely unknown. It is also controversial if JNK activity occurs in dying or in surviving cells. Signaling molecules of the Wnt and BMP families have been implicated in apoptosis-induced proliferation, but it is unclear if they are the only ones. To address these questions, we have developed an efficient assay for screening and identification of genes that regulate or mediate apoptosis-induced proliferation. We have identified a subset of genes acting upstream of JNK activity including Rho1. We also demonstrate that JNK activation occurs both in apoptotic cells as well as in neighboring surviving cells. In a genetic screen, we identified signaling by the EGFR pathway as important for apoptosis-induced proliferation acting downstream of JNK signaling. These data underscore the importance of genetic screening and promise an improved understanding of the mechanisms of apoptosis-induced proliferation.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a vast number of infections and deaths that deeply affect the world. When the virus encounters the host cell, it binds to angiotensin-converting enzyme 2, then the S protein of the virus is broken down by the transmembrane protease serine 2 with the help of furin, allowing the virus to enter the cell. The elevated inflammatory cytokines suggest that a cytokine storm, also known as cytokine release syndrome, may play a major role in the pathology of COVID-19. Therefore, the aim of this study is to investigate the relationship between circulating furin levels, disease severity, and inflammation in patients with SARS-CoV-2. A total of 52 SARS-CoV-2 patients and 36 healthy control participants were included in this study. SARS- CoV-2 patients were scored by the disease activity score. Serum furin, presepsin, and interleukin-6 (IL-6) levels were assessed using an enzyme-linked immunosorbent assay. The mean furin, presepsin, and IL-6 levels were significantly higher in the peripheral blood of SARS-CoV-2 compared to the controls ( p < 0.001). There were close positive relationship between serum furin and IL-6, furin and presepsin, and furin and disease severity ( r = 0.793, p < 0001; r = 0.521, p < 0.001; and r = 0,533, p < 0.001, respectively) in patients with SARS-CoV-2. These results suggest that furin may contribute to the exacerbation of SARS-CoV-2 infection and increased inflammation, and could be used as a predictor of disease severity in COVID-19 patients.

Abstract. The cancer stem cell hypothesis emphasizes that cancers are driven by cells having stem cell properties, and it is believed that cancer stem cells (CSCs) may be responsible for resistance against therapeutic approaches and for recurrent tumors. Since the biology of the normal breast requires large numbers of stem cells, it has been thought that breast stem cells play an important role in initiating breast cancer. A better characterization of breast CSCs appears to be an essential step to improve the understanding of the biology of breast cancer and its management. The scope of this study was to isolate breast CSCs from a breast cancer cell line (MCF-7) using cell surface markers, and to test whether these cells have any resistance to autophagic cell death mechanisms mediated by commonly used chemotherapies and hormonal therapies such as doxorubicin (adriamycin) and tamoxifen (anti-estrogen), respectively. For this purpose, the CD44 + / CD24 -/low MCF-7 breast cancer stem/progenitor cell population was isolated and treated with doxorubicin or tamoxifen and evaluated for their response to growth, autophagy and apoptosis. Our findings suggest that CD44 + /CD24 -/low cells were less sensitive to doxorubicin, but did not demonstrate a significant difference towards tamoxifen in regards to the induction of autophagy.

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