Overexpression of low‐density lipoprotein receptor and lipid accumulation in intestinal polyps in Min mice

Mutoh, Michihiro; Komiya, Masami; Teraoka, Naoya; Ueno, Tetsuo; Takahashi, Mami; Kitahashi, Tsukasa; Sügimura, Takashi; Wakabayashi, Keiji

doi:10.1002/ijc.24667

Cited by 26 publications

(22 citation statements)

References 24 publications

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“…In adenomatous polyposis coli ( Apc )-deficient Min mice, LDLR was overexpressed in the epithelia of the upper part of polyps where lipid droplets were observed. The expression levels of Ldlr mRNA in the intestinal polyps of Min mice were approximately three times higher compared to those in the non-tumor parts [45]. The expression level of LDLR was up-regulated in human lung adenocarcinoma A549 cells [46] and colorectal carcinoma cells [47].…”

Section: Discussionmentioning

confidence: 99%

Cholesterol-induced mammary tumorigenesis is enhanced by adiponectin deficiency: role of LDL receptor upregulation

Liu

Lam

et al. 2013

Oncotarget

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Adiponectin is an adipokine that can suppress the proliferation of various human carcinoma cells. Although its anti-tumor activities have been suggested by many clinical investigations and animal studies, the underlying mechanisms are not fully characterized. In MMTV-polyomavirus middle T antigen (MMTV-PyVT) transgenic mice models, reduced- or complete loss-of-adiponectin expression promotes mammary tumor development. The present study demonstrated that while tumor development in control MMTV-PyVT mice is associated with a progressively decreased circulating cholesterol concentration, adiponectin deficient MMTV-PyVT mice showed significantly elevated total- and low density lipoprotein (LDL)-cholesterol levels. Cholesterol contents in tumors derived from adiponectin deficient mice were dramatically augmented. High fat high cholesterol diet further accelerated the tumor development in adiponectin deficient PyVT mice. The protein levels of LDL receptor (LDLR) were found to be upregulated in adiponectin-deficient tumor cells. In human breast carcinoma cells, treatment with LDL-cholesterol or overexpressing LDLR elevates nuclear beta-catenin activity and facilitates tumor cell proliferation. On the other hand, adiponectin decreased LDLR protein expression in breast cancer cells and inhibited LDL-cholesterol-induced tumor cell proliferation. Both in vivo and in vitro evidence demonstrated a stimulatory effect of adiponectin on autophagy process, which mediated the down-regulation of LDLR. Adiponectin-induced reduction of LDLR was blocked by treatment with a specific inhibitor of autophagy, 3-methyladenine. In conclusion, the study demonstrates that adiponectin elicits tumor suppressive effects by modulating cholesterol homeostasis and LDLR expression in breast cancer cells, which is at least in part attributed to its role in promoting autophagic flux.

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Section: Discussionmentioning

confidence: 99%

Cholesterol-induced mammary tumorigenesis is enhanced by adiponectin deficiency: role of LDL receptor upregulation

Liu

Lam

et al. 2013

Oncotarget

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“…Low-density lipoprotein receptors (LDLRs) are the most exploited receptors for delivery across the BBB using peptides, because some of them are more expressed in the brain than in other organs [171] and overexpressed in some tumors [172]. LDLR targeting natural protein ligands, such as ApoB, ApoE fragments [173,174], and Angiopep-2, are widely used as a drug delivery peptide shuttle [170].…”

Section: Nanocarriers Nanoparticles and Vectorsmentioning

confidence: 99%

Overcoming the Blood–Brain Barrier. Challenges and Tricks for CNS Drug Delivery

2019

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Treatment of certain central nervous system disorders, including different types of cerebral malignancies, is limited by traditional oral or systemic administrations of therapeutic drugs due to possible serious side effects and/or lack of the brain penetration and, therefore, the efficacy of the drugs is diminished. During the last decade, several new technologies were developed to overcome barrier properties of cerebral capillaries. This review gives a short overview of the structural elements and anatomical features of the blood–brain barrier. The various in vitro (static and dynamic), in vivo (microdialysis), and in situ (brain perfusion) blood–brain barrier models are also presented. The drug formulations and administration options to deliver molecules effectively to the central nervous system (CNS) are presented. Nanocarriers, nanoparticles (lipid, polymeric, magnetic, gold, and carbon based nanoparticles, dendrimers, etc.), viral and peptid vectors and shuttles, sonoporation and microbubbles are briefly shown. The modulation of receptors and efflux transporters in the cell membrane can also be an effective approach to enhance brain exposure to therapeutic compounds. Intranasal administration is a noninvasive delivery route to bypass the blood–brain barrier, while direct brain administration is an invasive mode to target the brain region with therapeutic drug concentrations locally. Nowadays, both technological and mechanistic tools are available to assist in overcoming the blood–brain barrier. With these techniques more effective and even safer drugs can be developed for the treatment of devastating brain disorders.

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“…Mitochondria are vital organelles in many cellular processes, including cellular respiration, energy expenditure and apoptosis. Their ability to affect energy expenditure and body weight in conjunction with cell death may play an important role in obesity‐related cancer pathways (76). Indeed, mitochondrial content and function have been found to decrease with age, physical inactivity and metabolic diseases associated with insulin resistance (77), via a variety of proposed mechanisms (reviewed in (78)).…”

Section: Potential Role Of Mitochondria In the Onset And Therapy Of Omentioning

confidence: 99%

Mechanisms linking obesity, inflammation and altered metabolism to colon carcinogenesis

2012

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Due to its prevalence, obesity is now considered a global epidemic. It is linked to increased risk of colorectal cancer, the third most common cancer and the second leading cause of death among adults in Western countries. Obese adipose tissue differs from lean adipose tissue in its immunogenic profile, body fat distribution and metabolic profile. Obese adipose tissue releases free fatty acids, adipokines and many pro-inflammatory chemokines. These factors are known to play a key role in regulating malignant transformation and cancer progression. Obese adipose tissue is infiltrated by macrophages that participate in inflammatory pathways activated within the tissue. Adipose tissue macrophages consist of two different phenotypes. M1 macrophages reside in obese adipose tissue and produce pro-inflammatory cytokines, and M2 macrophages reside in lean adipose tissue and produce anti-inflammatory cytokines, such as interleukin-10 (IL-10). The metabolic networks that confer tumour cells with their oncogenic properties, such as increased proliferation and the ability to avoid apoptosis are still not well understood. We review the interactions between adipocytes and immune cells that may alter the metabolism towards promotion of colorectal cancer.

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Overexpression of low‐density lipoprotein receptor and lipid accumulation in intestinal polyps in Min mice

Cited by 26 publications

References 24 publications

Cholesterol-induced mammary tumorigenesis is enhanced by adiponectin deficiency: role of LDL receptor upregulation

Cholesterol-induced mammary tumorigenesis is enhanced by adiponectin deficiency: role of LDL receptor upregulation

Overcoming the Blood–Brain Barrier. Challenges and Tricks for CNS Drug Delivery

Mechanisms linking obesity, inflammation and altered metabolism to colon carcinogenesis

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