LSR (Lipolysis Stimulated Lipoprotein Receptor)

MDR1 inhibitor verapamil and MDR1-targeted siRNA were used to evaluate the functional impact of LSR-induced MDR1. In contrast, knockout of LSR expression in MDA-MB-468 cells, which express higher levels of LSR, significantly sensitized the cells to doxorubicin-induced growth inhibition and apoptosis. Our data demonstrated that LSR overexpression promotes TNBC cell proliferation and invasion, and upregulation of MDR1 in these cells renders them resistant to doxorubicin, suggesting that targeting LSR could be a useful strategy to overcome chemoresistance in TNBC.

Notably, no off-target effects or systemic toxicity were observed in animal models during or after treatment. This study highlights LSR as a promising therapeutic target and the anti-LSR mAb and ADC as potential targeted therapies for TNBC.

These findings demonstrate the effects of tricellular tight junction inhibition on disrupting the BTB, enhancing CNS drug delivery, and improving rodent glioma survival. This study demonstrates that Angubindin-1, a targeted modulator of tricellular tight junction protein Angulin-1/LSR, transiently disrupts BTB integrity to enhance chemotherapy delivery and prolong survival in glioma-bearing rats.

Genes TAP2, PLD4, P2RX7, ALDH9A1, SLC11A2, ADM, C3, AVP, RXFP3, VIP, NKX2-1, SLC11A2 and HMOX1 may play an important regulatory role on GABAergic neurons, neuroactive ligand-receptor and ferroptosis pathways related to neuron, immune, and stress behaviour, and in turn affects social rank. Fumaric, l-glutamic and 4-Oxoproline, may regulate social rank through the "alanine, aspartate and glutamate metabolism" and "arginine biosynthesis".

Low LSR expression is associated with adverse prognosis in glioma patients. By modulating FOXO3a, LSR overexpression suppresses glioma cell proliferation and invasion.

A253 cells were treated with human recombinant TNFα with or without HDAC inhibitor trichostatin A (TSA) and quisinostat (JNJ-26481585). The tricellular signaling pathway JNK inhibitor SP600125 and Hippo pathway MST1/2 inhibitor XMU-MP-1 prevented the apoptosis induced by treatment using TNFα or LSR-N-ab with HDAC inhibitors. Our findings indicated that treatment with TNFα or LSR-N-ab with HDAC inhibitors might be useful in the therapy for human SDC by enhancing apoptosis.

We demonstrated that lipids are taken up into gastric cancer cells via LSR and cause an increase in β-oxidation, resulting in the promotion of cancer progression. Controlling LSR-mediated lipid metabolism may be a novel therapeutic strategy for gastric cancer.

In 2D and 2.5D cultures, treatment with β-estradiol with or without EGF or TGF-β decreased CGN expression and the epithelial permeability barrier and enhanced cell migration, and pretreatment with EW7197+AG1478, U0126 or an anti-IL-6 antibody prevented this. In conclusion, CGN, with tTJ proteins might suppress the malignancy of human EEC and its complex proteins are sensitive to estrogen and growth factors derived from stromal cells.

These findings show that LSR negatively regulates T-cell immune activity. LSR targeting could provide immune checkpoint inhibitors for cancer immunotherapy.

The developed LSR-ADC demonstrated a significant antitumor activity against LSR-positive EOC cell lines and tumors. Our preclinical data support the use of the LSR-ADC as a novel therapy for patients with LSR-positive ovarian cancer.