Last update 01 Nov 2024

LSR

Last update 01 Nov 2024

Basic Info

Synonyms

Angulin-1, ILDR3, lipolysis stimulated lipoprotein receptor

+ [4]

Introduction

Probable role in the clearance of triglyceride-rich lipoprotein from blood. Binds chylomicrons, LDL and VLDL in presence of free fatty acids and allows their subsequent uptake in the cells (By similarity). Maintains epithelial barrier function by recruiting MARVELD2/tricellulin to tricellular tight junctions (By similarity).

Drugs associated with LSR

JP2024068984

Patent Mining

Target

LSR

Mechanism-

Active Org.

Iwate Medical University

Originator Org.

Iwate Medical University

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

WO2024101382

Patent Mining

Target

LSR

Mechanism-

Active Org.

Iwate Medical University

Originator Org.

Iwate Medical University

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with LSR

100 Translational Medicine associated with LSR

0 Patents (Medical) associated with LSR

215

Literatures (Medical) associated with LSR

01 Nov 2024·Gastric Cancer

Lipolysis-stimulated lipoprotein receptor promote lipid uptake and fatty acid oxidation in gastric cancer

Article

Author: Kawai, Kunihiko ; Makino, Tomoki ; Yokouchi, Takashi ; Nakajima, Kiyokazu ; Momose, Kota ; Kurokawa, Yukinori ; Naka, Tetsuji ; Kawabata, Kota ; Saito, Takuro ; Yamamoto, Kazuyoshi ; Eguchi, Hidetoshi ; Serada, Satoshi ; Tanaka, Koji ; Yamashita, Kotaro ; Takahashi, Tsuyoshi ; Fujimoto, Minoru ; Doki, Yuichiro

BACKGROUNDLipolysis-stimulated lipoprotein receptor (LSR), a lipid receptor, is associated with cancer progression. However, detailed effects on intracellular metabolism are unclear. We aimed to elucidate the mechanism of LSR-mediated lipid metabolism in gastric cancer.METHODSWe investigated lipid metabolic changes induced by lipoprotein administration in gastric cancer cells and evaluated the significance of LSR expression and lipid droplets formation in gastric cancer patients. The efficacy of inhibiting β-oxidation in gastric cancer cells was also examined in vitro and vivo.RESULTSIn gastric cancer cells, LSR promoted cellular uptake of lipoprotein and cell proliferation. Furthermore, the inhibition of LSR in gastric cancer cells expressing high levels of LSR counteracted both effects. Immunohistochemical analysis of human gastric cancer tissues showed that the increase in lipid droplets via LSR is a factor that influences prognosis. Lipidomics analysis of LSR-high-expressing gastric cancer cells revealed an increase in β-oxidation. Based on these results, we used etomoxir, a β-oxidation inhibitor, and found that it inhibited cell proliferation as well as the suppression of LSR. Similarly, in a mouse xenograft model of LSR-highly expressing gastric cancer cells, the tumor growth effect of high-fat diet feeding was counteracted by etomoxir, consistent with the Ki-67 labeling index.CONCLUSIONSWe 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.

01 Oct 2024·Current Biology

Mechanosensitive recruitment of Vinculin maintains junction integrity and barrier function at epithelial tricellular junctions

Article

Author: Miller, Ann L. ; Koning, Katherine M. ; Iseler, Jolene ; van den Goor, Lotte ; Miller, Ann L ; Koning, Katherine M

Apical cell-cell junctions, including adherens junctions and tight junctions, adhere epithelial cells to one another and regulate selective permeability at both bicellular junctions and tricellular junctions (TCJs). Although several specialized proteins are known to localize at TCJs, it remains unclear how actomyosin-mediated tension transmission at TCJs contributes to the maintenance of junction integrity and barrier function at these sites. Here, utilizing the embryonic epithelium of gastrula-stage Xenopus laevis embryos, we define a mechanism by which the mechanosensitive protein Vinculin helps anchor the actomyosin network at TCJs, thus maintaining TCJ integrity and barrier function. Using an optogenetic approach to acutely increase junctional tension, we find that Vinculin is mechanosensitively recruited to apical junctions immediately surrounding TCJs. In Vinculin knockdown (KD) embryos, junctional actomyosin intensity is decreased and becomes disorganized at TCJs. Using fluorescence recovery after photobleaching (FRAP), we show that Vinculin KD reduces actin stability at TCJs and destabilizes Angulin-1, a key tricellular tight junction protein involved in regulating barrier function at TCJs. When Vinculin KD embryos are subjected to increased tension, TCJ integrity is not maintained, filamentous actin (F-actin) morphology at TCJs is disrupted, and breaks in the signal of the tight junction protein ZO-1 signal are detected. Finally, using a live imaging barrier assay, we detect increased barrier leaks at TCJs in Vinculin KD embryos. Together, our findings show that Vinculin-mediated actomyosin organization is required to maintain junction integrity and barrier function at TCJs and reveal new information about the interplay between adhesion and barrier function at TCJs.

01 Sep 2024·Environmental Research

Effects of the quorum sensing related luxS gene and lsr operon on Klebsiella michiganensis resisting copper stress

Article

Author: Wang, Xinlong ; Gao, Ya ; Peng, Dongyu ; Lin, Shanshan

Industrial wastewater is a major environmental concern due to its high copper content, which poses significant toxicity to microbial life. Autoinducer-2 (AI-2) can participate in the inter- and intra-species communication and regulate the physiological functions of different bacterial species by producing AI-2 signal molecules. However, there are few research reports on the luxS gene and lsr operon functions for AI-2 in bacteria with a certain tolerance to copper. This study delves into the potential of quorum sensing mechanisms, particularly the AI-2 system, for enhancing microbial resistance to copper toxicity in Klebsiella michiganensis (KM). We detail the critical roles of the luxS gene in AI-2 synthesis and the lsr operon in AI-2 uptake, demonstrating their collective impact on enhancing copper resistance. Our findings show that mutations in the lsr operon, alongside the knockout of the luxS gene in KM strain (KMΔluxSΔlsr), significantly impair the strain's motility (p < 0.0001) and biofilm formation (p < 0.01), underscoring the operon's role in AI-2 transport. These genetic insights are pivotal for developing bioremediation strategies aimed at mitigating copper pollution in wastewater. By elucidating the mechanisms through which KM modulates copper resistance, this study highlights the broader ecological significance of leveraging microbial quorum sensing pathways for sustainable wastewater management.

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