Understanding cancer from an evolutionary perspective: high-risk reprogramming of genome-damaged stem cells

Academia Medicine, Год журнала: 2024, Номер 1(1)

Опубликована: Янв. 31, 2024

Background: One of the most astounding discoveries recent times is recognition that cancer embodies a transition from higher level metazoan cell organization to more foundational premetazoic state.This shift steered by genes housed within ancestral genome compartment, pervasive across all genomes, encompassing humans, and governed gene regulatory network.This work aims highlight emerging field evolutionary biology (ECCB), which points deep homology between protist life cycles tracing back common ancestor amoebozoans, metazoans, fungi (AMF).The ECCB analysis reveals essence non-gametogenic germline AMF ancestor, serves as blueprint for germlines stem lineages controls cycle cancer.Every germ lineage humans metazoans traces its this Urgermline, transmitting crucial processes such asymmetric cycling, differentiation, stemness, phenomena like germ-to-soma GST soma-to-germ (aka epithelial-mesenchymal EMT MET) their subsequent descendants.Oxygen-sensitive cells suffer DNA doublestrand breaks due stress oxygen ranges reminiscent hyperoxia, leading senescence.Cells can overcome senescence proliferate defective symmetric division, paving way malignancy polyploid giant cancers.Conclusions: Understanding origins may help break some logjams in prevention open up new therapeutic pathways.

Язык: Английский

R-spondins secreted by human pancreas-derived mesenchymal stromal cells support pancreatic organoid proliferation

Cellular and Molecular Life Sciences, Год журнала: 2025, Номер 82(1)

Опубликована: Март 20, 2025

Mesenchymal stromal cells (MSC) play a critical role in the stem cell niche, specialized microenvironment where reside and interact with surrounding extracellular matrix components. Within MSC offer structural support, modulate inflammatory response, promote angiogenesis release specific signaling molecules that influence behavior, including self-renewal, proliferation differentiation. In epithelial tissues such as intestine, stomach liver, act an important source of cytokines growth factors, but not much is known about their pancreas. Our group has established standardized technology for generation pancreatic organoids. Herein, we investigated mesenchymal regulation human organoid growth, using this 3D model co-culture system. We particularly focused on capacity to produce R-spondin which are considered regulators growth. propose development complex vitro system combines cells, thereby promoting assembloid new research era.

Язык: Английский

Niche-adjacent Type IV collagen promotes GLP-1/Notch receptor activation in the C. elegans germline

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Май 8, 2024

Basement membranes are thin and dense proteinaceous layers of specialized extracellular matrix that surround tissues to maintain their structure function¹. With age, chronic inflammation typically stiffens this basement membrane in a phenomenon called fibrosis, the progression which is reflected by increasing levels membrane’s main component, type IV collagen (COL IV)^2,3. Tissue fibrosis elevated Notch signaling two co-occurring hallmarks many inflammation-linked diseases, including cancer^3-6. Many reasoned may be consequence signaling, belief has led targeting antifibrotic therapy attempts^7,8,9. Yet, in vivo relationship between activity not been clearly defined. Here, we show EMB-9/COL accumulation adjacent C. elegans germline stem cell niche promotes GLP-1/Notch receptor activation germline cells. Increased therefore high COL contents. Moreover, find reducing leads generalized dramatic increase levels, thereby fibrosis. The comes along with inflammaging act as root cause for cancer promoting perhaps more widely, other ligand-receptor interactions.

Язык: Английский