LRP1 expression

We show that two different immunogenic HSPs that bind CD91 differentially utilize AXL and Fgr and activate distinct programming of dendritic cells, which is important for the varied immunological responses that tumors evoke. Overall, these findings describe an innate sensing mechanism of nascent tumors by dendritic cells, resulting in initiation of anti-tumor responses via the HSP-CD91 axis.

Our results show an elaborate and synchronized division of labor of APCs in the successful elimination of cancer cells via CD91. We predict that the specialized functions of APC subsets can be harnessed for immunotherapy of disease.

LRP1 knockdown inhibited CD36 gene expression in HepG2 and BxPC-3 cells. LRP1 knockdown inhibited the proliferation, invasion and migration of GI cancer cells, suggesting that LRP1 may be a novel target for treatment of GI tumors.

Our study suggests that LRP1 may be a potential prognostic biomarker and therapeutic target in BLCA. Further research on LRP1 may improve BLCA precision medicine and enhance the efficacy of immune checkpoint blockade therapy.

SNPs rs746886209 and rs758644665 were indicated by both SIFT and PolyPhen-2 to have deleterious effects on CD91 folding and patients with these mutations had below average immune infiltration. While these data are currently correlative, we have developed an in vitro model to obtain proof of concept.

We identified YO-2 as a novel p53 inducer in melanoma cells. Cotreatment of YO-2 with doxorubicin blocked tumor growth in vivo and in a murine melanoma model, suggesting that YO-2 exerts anti-melanoma effects alone or in combination with conventional myelosuppressive drugs.

LRP1 modulates metabolic disease manifestation, inflammation, and differentiation in a cell-dependent, time-dependent, and tissue-dependent manner. Whether LRP1 expression is protective or pathogenic is dependent on its interaction with specific ligands and intracellular proteins, which in turn is dependent on the cell type and the microenvironment where these cells reside.

This study has provided valuable insights into transcriptomic heterogeneity and the global cellular network in the TME, which coordinately functions to promote the progression of GBC with ErbB pathway mutations; thus unveiling novel cellular and molecular targets for cancer therapy.