Scavenger receptor class B type I regulates cellular cholesterol metabolism and cell signaling associated with breast cancer development

Danilo, Christiane; Gutiérrez-Pajares, Jorge L.; Mainieri, Maria Antonietta; Mercier, Isabelle Le; Lisanti, Michael P.; Frank, Philippe G.

doi:10.1186/bcr3483

Cited by 117 publications

(156 citation statements)

References 55 publications

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“…The second mechanism is based on the capacity of SR-B1 to trigger an intracellular signaling cascade that leads to increased tumor cell proliferation. In this regard, activation of the PI3K/AKT pathway by SR-B1 ligands provides an essential survival signal for tumor cells [84,85]. A third mechanism of SR-B1 to promote tumor growth is by the inhibition of acute inflammation [73,74].…”

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confidence: 99%

“…SR-B1 has been implicated in several biological processes such as apoptosis [86,87] entry through TRPC3 channels, leading to dampened cytokine production in response to CpG via TLR9 activation [90]. Disrupting SR-B1 function by genetic or chemical inhibitors may decrease tumor cell malignancy [85,91]. The main mechanisms of action proposed for these therapeutic interventions are the reduced availability of cholesterol and the decreased activation of the PI3K/AKT pathway.…”

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confidence: 99%

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Exploiting scavenger receptors in cancer immunotherapy: Lessons from CD5 and SR‐B1

et al. 2017

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Scavenger receptors (SRs) are structurally heterogeneous cell surface receptors characterized by their capacity to remove extraneous or modified self-macromolecules from circulation, thus avoiding the accumulation of noxious agents in the extracellular space. This scavenging activity makes SRs important molecules for host defense and homeostasis. In turn, SRs keep the activation of the steady-state immune response in check, and participate as co-receptors in the priming of the effector immune responses when the macromolecules are associated with a threat that might compromise host homeostasis. Therefore, SRs built up sophisticated sensor mechanisms controlling the immune system, which may be exploited to develop novel drugs for cancer immunotherapy. In this review, we focus on the regulation of the anti-tumor immune response by two paradigmatic SRs: the lymphocyte receptor CD5 and the more broadly distributed scavenger receptor class B type 1 (SR-B1). Cancer immunity can be boosted by blockade of SRs working as immune checkpoint inhibitors (CD5) and/or by proper engagement of SRs working as innate danger receptor (SR-B1). Thus, these receptors illustrate both the complexity of targeting SRs in cancer immunotherapy and also the opportunities offered by such an approach. Keywords:Cancer immunotherapy r CD5 r Danger signal r Immune-checkpoint r Scavenger receptor r Scavenger receptor class B type 1 r Toll-like receptors IntroductionThe cancer-immunity cycle can be subverted by tumors at many steps, thus novel therapeutic interventions should be considered for all these possibilities [1]. This cycle starts with the release of tumor antigens and their subsequent capture by professional antigen-presenting cells (mainly, dendritic cells; DCs) for the activation of effector cells of the innate and adaptive immune Correspondence: Dr. Pedro Berraondo e-mail: pberraondol@unav.es system. This is a highly regulated process aimed at maintaining the integrity of the host without inducing significant side effects (e.g., inflammation or autoimmunity) [2]. Tissue homeostasis involves phagocytic processes to remove the excess of native or modified molecules from unviable or stressed cells, as well as from invading microbial agents [3]. Such molecules include lipids, whose intracellular levels should be carefully controlled to sustain proper cell metabolism; endogenous glyco-and lipo-proteins, damaged or * These authors contributed equally to this work. * * These authors are senior co-authors of this work. [4,5]. This phagocytic activity should be coupled to an alarm signal system that awakens other effector mechanisms of the immune system when the tissue damage cannot be controlled by the removal of the endogenous or exogenous molecules. To this end, the immune system has a myriad of specialized soluble or membrane-bound receptors called pattern recognition receptors (PRRs). These PRRs are non-polymorphic, nonclonally distributed, and germ-line encoded receptors recognizing microorganism-associated molecular patterns (MAMPs) -tha...

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confidence: 99%

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confidence: 99%

Exploiting scavenger receptors in cancer immunotherapy: Lessons from CD5 and SR‐B1

et al. 2017

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“…Multiple studies have found that SR-BI is implicated in the regulation of diverse tumor cell biology, including tumor cell proliferation, apoptosis, migration and invasion (7,8). The present study analyzed the expression of SR-BI in multiple gastric adenocarcinoma specimens and found that SR-BI immunoreactivity was present in 69% of cases.…”

Section: Discussionmentioning

confidence: 88%

“…Pronounced expression of SR-BI was observed in a variety of carcinomas, including hepatoma, prostate, breast, colorectal, pancreatic, ovarian, and nasopharyngeal cancer (9)(10)(11)(12). Moreover, SR-BI has been demonstrated to exert a profound influence on the proliferation, migration and invasion of breast and prostate cancer cells (7,8). In human stomach, Lobo et al (13) reported that SR-BI was not detected in epithelial, parietal, mucous and endocrinal cells.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, SR-BI serves a role in sepsis, adaptive immune and hepatitis C virus entry (4)(5)(6). It is becoming increasingly apparent that SR-BI serves a role in cancer development (7,8). Pronounced expression of SR-BI was observed in a variety of carcinomas, including hepatoma, prostate, breast, colorectal, pancreatic, ovarian, and nasopharyngeal cancer (9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

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Low scavenger receptor classï¿½B typeï¿½I expression is associated with gastric adenocarcinoma tumor aggressiveness

Wang

Yuan

et al. 2018

Oncol Lett

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Abstract. Scavenger receptor class B type I (SR-BI), a well-documented high-density lipoprotein receptor, has been implicated in the development and progression of human cancer. However, little is known regarding the expression profile and clinical value of SR-BI in gastric adenocarcinoma. In the present study immunohistochemistry analysis was performed on a well-annotated gastric adenocarcinoma tissue microarray to investigate the association between SR-BI expression and clinicopathological parameters or patient outcome. The results revealed that SR-BI expression was detected in 69% of the 84 gastric adenocarcinomas. Moreover, a significant association was observed between low SR-BI expression and poor histological grade, higher Tumor-Node-Metastasis T stage, higher N stage and diffuse type carcinoma. Low SR-BI expression was also significantly associated with a shorter overall survival time in patients with gastric adenocarcinoma, although it was not an independent prognostic factor. Overall, the results of the present study demonstrated that SR-BI was possibly involved in gastric carcinogenesis and could be used as a biomarker to predict malignancy of gastric adenocarcinoma.

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High‐density lipoprotein functionality and breast cancer: A potential therapeutic target

Samadi

Mobarhan

Mohammadpour

et al. 2018

J of Cellular Biochemistry

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Breast cancer is a major cause of death globally, and particularly in developed countries. Breast cancer is influenced by cholesterol membrane content, by affecting the signaling pathways modulating cell growth, adherence, and migration. Furthermore, steroid hormones are derived from cholesterol and these play a key role in the pathogenesis of breast cancer. Although most findings have reported an inverse association between serum high‐density lipoprotein (HDL)‐cholesterol level and the risk of breast cancer, there have been some reports of the opposite, and the association therefore remains unclear. HDL is principally known for participating in reverse cholesterol transport and has an inverse relationship with the cardiovascular risk. HDL is heterogeneous, with particles varying in composition, size, and structure, which can be altered under different circumstances, such as inflammation, aging, and certain diseases. It has also been proposed that HDL functionality might have a bearing on the breast cancer. Owing to the potential role of cholesterol in cancer, its reduction using statins, and particularly as an adjuvant during chemotherapy may be useful in the anticancer treatment, and may also be related to the decline in cancer mortality. Reconstituted HDLs have the ability to release chemotherapeutic drugs inside the cell. As a consequence, this may be a novel way to improve therapeutic targeting for the breast cancer on the basis of detrimental impacts of oxidized HDL on cancer development.

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Scavenger receptor class B type I regulates cellular cholesterol metabolism and cell signaling associated with breast cancer development

Cited by 117 publications

References 55 publications

Exploiting scavenger receptors in cancer immunotherapy: Lessons from CD5 and SR‐B1

Exploiting scavenger receptors in cancer immunotherapy: Lessons from CD5 and SR‐B1

Low scavenger receptor classï¿½B typeï¿½I expression is associated with gastric adenocarcinoma tumor aggressiveness

High‐density lipoprotein functionality and breast cancer: A potential therapeutic target

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