Screening of Ceramide-Dependent Exosomal Cargoes in Terms of their Vesicular Abundance in Colorectal Cancer

Colorectal cancer (CRC) is one of the most common malignancies worldwide and a leading cause of cancer-related mortalities. It originates from the epithelial cells of the colon or rectum, evolving through various genetic and epigenetic changes. CRC development is often associated with the adenoma carcinoma sequence, where benign polyps transform into malignant tumors over time. CRC metastasis is largely regulated by the secretome components released from the cancer cells. Neutral sphingomyelinase 2 (nSMase2) is potentially related to secretomes due to its role in exosome biogenesis which include the release of exosomal cargoes. This report highlights the significance of studying ceramide-dependent exosomal cargoes to enhance our understanding of colorectal cancer metastasis via Exosomes. Exosomes, the small extracellular vesicles secreted by cells, transport a variety of molecules, including proteins, nucleic acids, and lipids, that can affect disease progression. Ceramide-dependent exosomal cargoes are those that are reduced at their exosomal level upon blocking nSMase-2. Current study focusses on screening the ceramide-dependent exosomal cargoes that are highly reported in vesicular pools of “Vesiclespedia” database in regards to CRC. The finding of the study underscores the role of selected proteins classes that are involved in mediating intercellular communication between, providing insights into the molecular keystones of metastasis. The study highlights the role of Ceramide-dependent Exosomal Cargoes in promoting CRC metastasis through exosome-mediated intercellular communication and intracellular signaling modulation, suggesting potential therapeutic targets for managing CRC progression. From overall observation we have selected SPRED2 and LAMT as representative understudied proteins, given their minimal or absent documentation in CRC exosome literature. The inclusion of these low-frequency candidates aims to uncover potentially novel roles and functional significance that may have been previously overlooked in CRC pathogenesis