C. elegans Germline as Three Distinct Tumor Models

Both extrinsic signaling and intrinsic regulation are critical for maintaining cellular homeostasis, and their dysregulation is often associated with tumorigenesis and human diseases. This report outlines three distinct C. elegans tumor models resulting from mutations in conserved extrinsic signaling pathways (e.g., Notch signaling) and intrinsic RNA-binding proteins (e.g., GLDs and PUF). These models highlight how C. elegans Notch signaling and RNA-binding proteins contribute to tumor initiation, progression, and suppression, depending on the cellular context. Therefore, in addition to targeting oncogenic signaling pathways, directing attention toward RNA-binding proteins holds great potential for a tumor-type-specific therapy approach. Tumor cells display abnormal growth and division, avoiding the natural process of cell death. These cells can be benign (non-cancerous growth) or malignant (cancerous growth). Over the past few decades, numerous in vitro or in vivo tumor models have been employed to understand the molecular mechanisms associated with tumorigenesis in diverse regards. However, our comprehension of how non-tumor cells transform into tumor cells at molecular and cellular levels remains incomplete. The nematode C. elegans has emerged as an excellent model organism for exploring various phenomena, including tumorigenesis. Although C. elegans does not naturally develop cancer, it serves as a valuable platform for identifying oncogenes and the underlying mechanisms within a live organism. In this review, we describe three distinct germline tumor models in C. elegans, highlighting their associated mechanisms and related regulators: (1) ectopic proliferation due to aberrant activation of GLP-1/Notch signaling, (2) meiotic entry failure resulting from the loss of GLD-1/STAR RNA-binding protein, (3) spermatogenic dedifferentiation caused by the loss of PUF-8/PUF RNA-binding protein. Each model requires the mutations of specific genes (glp-1, gld-1, and puf-8) and operates through distinct molecular mechanisms. Despite these differences in the origins of tumorigenesis, the internal regulatory networks within each tumor model display shared features. Given the conservation of many of the regulators implicated in C. elegans tumorigenesis, it is proposed that these unique models hold significant potential for enhancing our comprehension of the broader control mechanisms governing tumorigenesis.