Entosis: From Cell Biology to Clinical Cancer Pathology

Abstract

Entosis is a phenomenon, in which one cell enters a second one. New clinico-histopathological studies of entosis prompted us to summarize its significance in cancer. It appears that entosis might be a novel, independent prognostic predictor factor in cancer histopathology. We briefly discuss the biological basis of entosis, followed by a summary of published clinico-histopathological studies on entosis significance in cancer prognosis. The correlation of entosis with cancer prognosis in head and neck squamous cell carcinoma, anal carcinoma, lung adenocarcinoma, pancreatic ductal carcinoma and breast ductal carcinoma, is shown. Numerous entotic figures are associated with a more malignant cancer phenotype and poor prognosis in many cancers. We also showed that some anticancer drugs could induce entosis in cell culture, even as an escape mechanism. Thus, entosis is likely beneficial for survival of malignant cells, i.e., an entotic cell can hide from unfavourable factors in another cell and subsequently leave the host cell remaining intact, leading to failure in therapy or cancer recurrence. Finally, we highlight the potential relationship of cell adhesion with entosis in vitro, based on the model of the BxPc3 cells cultured in full adhesive conditions, comparing them to a commonly used MCF7 semiadhesive model of entosis.

Classification of Cell-in-Cell Structures: Different Phenomena with Similar Appearance

“…However, there is growing interest in CICs as they could be a novel key factor that regulates cell survival and death. It appears that CICs have prognostic significance in several types of cancer [7]. Moreover, we predict that modulation of this process may be used in the future as a novel therapeutic approach that could influence prognosis, especially in oncological patients.…”

“…It can also be associated with cancer progression and worse prognosis [5,6]. As we summarized before [7], the CIC process may be modulated by external factors, including: nutrient deprivation [2,8,9], hypoxemia [10], infection, non-adhesive conditions [11,12], and/or presence of distinct chemotherapeutic agents in the extracellular milieu [13,14].…”

Exploring rare cellular activity in more than one million cells by a transscale scope

“…In the image sequence, we also found another rare phenomenon that a very small fraction of the cells cannibalized their neighboring cells. This phenomenon, called entosis, was first studied on epithelial cells detached from extra-cellular matrix 36 and recently its function in cancer has been well studied 37 . Cannibalization of D. discoideum has been discussed for much longer than in other cells, but it was understood as a process when a giant cell engulfs hundreds of neighboring cells to form a macrocyst 38 , 39 .…”

Network Analysis Identifies Drug Targets and Small Molecules to Modulate Apoptosis Resistant Cancers

“…Intriguingly, we observed RHOA (down, entotic cell death) as a common drug target in GBM and SCLC. Entosis regulates the malignant cells [ 35 ]. We found the following TFs targeting drug targets: TF ZNF100 targets FANCD2 and BACH1, KLF1, ZBTB14 interacts with NCOA4 in COAD.…”