2026-10-10T14:26:24Z https://api.figshare.com/v2/oai

oai:figshare.com:article/32639673 2026-10-01T16:38:01Z portal_1172 item_type_8 month_year_10_2026

Mechanisms and models of Gremlin1 signaling in human disease Zhichun Gao (9621230) PUREID: 592158085 GREM1 cancer research cell signaling cell biology BMP antagonist colorectal cancer Gremlin1 (GREM1) is a secreted glycoprotein that regulates embryonic development and influences several human diseases by antagonising bone morphogenetic proteins (BMPs). It prevents BMPs from interacting with their receptors, crucial for kidney and limb formation. Disruptions in this signaling may cause developmental anomalies like renal agenesis and abnormal digit formation. GREM1 is also linked to fibrosis in the kidney and lung, chronic pancreatitis, and cancers of the colon, lung, and cervix. In studies using GREM1-FITC, GREM1 was found to enter colorectal and cervical cancer cells via clathrin-mediated, caveolin-mediated, and dynamin-mediated endocytosis. It localised to early endosomes post-uptake and was partly re-secreted. The glycosylation of GREM1 isn't necessary for its uptake; however, heparin sulphate proteoglycans (HSPGs) are essential. Additionally, GREM1 influences insulin signaling in HeLa cells and activates the Fibroblast growth factor receptor 1 (FGFR1) pathway, enhancing its downstream signaling. This suggests GREM1's involvement in cervical and colorectal cancer development through alternative signaling pathways, independent of BMP antagonism. To understand GREM1's cellular interactions further, a proximity biotinylation method using GREM1-TurboID fusion protein identified potential GREM1 binding partners on the plasma membrane and intracellularly, requiring further study to confirm these interactions. This thesis presents novel insights into GREM1's role in cancer by detailing its mechanisms of uptake, secretion, and interaction with other proteins, laying groundwork for potential new cancer treatments by targeting GREM1-related pathways. 2026-10-01T16:38:01Z Text Thesis 10.17034/32639673.v1 https://figshare.com/articles/thesis/Mechanisms_and_models_of_Gremlin1_signaling_in_human_disease/32639673 All Rights Reserved