Oncogenic role and therapeutic target of leptin signaling in colorectal cancer

Zhou, Weiqiang; Tian, Yuwang; Gong, Huan; Guo, Shanchun; Luo, Chengyu

doi:10.1517/14728222.2014.926889

Cited by 16 publications

(12 citation statements)

References 146 publications

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“…Leptin inhibition resulted in a decrease in the growth of tumours in animal and human studies [30]. Although antibodies against leptin receptors have been developed, these have yet to be tested as a CRC treatment [31].…”

Section: Leptinmentioning

confidence: 99%

The prognostic and therapeutic role of hormones in colorectal cancer: a review

et al. 2018

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Colorectal cancer (CRC) is one of the commonest cancers in Western society with a poor prognosis in patients with advanced disease. Targeted therapy is of increasing interest and already, targeted hormone treatment for breast and prostate cancer has improved survival. The aim of this literature review is to summarise the role of hormones in CRC prognosis and treatment. A literature review of all human and animal in vivo and in vitro studies in the last 20 years, which assessed the role of hormones in CRC treatment or prognosis, was carried out. The hormones described in this review have been subdivided according to their secretion origin. Most of the studies are based on in vitro or animal models. The main findings point to adipokines, insulin and the insulin growth factor axis as key players in the link between obesity, type 2 diabetes mellitus and a subset of CRC. Gut-derived hormones, especially uroguanylin and guanylin are being increasingly investigated as therapeutic targets, with promising results. Using hormones as prognostic and therapeutic markers in CRC is still in the preliminary stages for only a fraction of the hormones affecting the GIT. In light of the increasing interest in tailoring treatment strategies, hormones are an important area of focus in the future of CRC management.

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Section: Leptinmentioning

confidence: 99%

The prognostic and therapeutic role of hormones in colorectal cancer: a review

et al. 2018

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“…These phenomena lead to the deregulation of leptin signaling, thereby significantly contributing to HCC progression through its crosstalk with multiple signaling pathways, as discussed in breast cancer 47 or colorectal cancer. 68 …”

Section: Interaction Between Leptin Signaling and Oncogenic Pathways mentioning

confidence: 99%

Leptin signaling molecular actions and drug target in hepatocellular carcinoma

Jiang¹,

Sun²,

Sun³

2014

DDDT

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Previous reports indicate that over 13 different tumors, including hepatocellular carcinoma (HCC), are related to obesity. Obesity-associated inflammatory, metabolic, and endocrine mediators, as well as the functioning of the gut microbiota, are suspected to contribute to tumorigenesis. In obese people, proinflammatory cytokines/chemokines including tumor necrosis factor-alpha, interleukin (IL)-1 and IL-6, insulin and insulin-like growth factors, adipokines, plasminogen activator inhibitor-1, adiponectin, and leptin are found to play crucial roles in the initiation and development of cancer. The cytokines induced by leptin in adipose tissue or tumor cells have been intensely studied. Leptin-induced signaling pathways are critical for biological functions such as adiposity, energy balance, endocrine function, immune reaction, and angiogenesis as well as oncogenesis. Leptin is an activator of cell proliferation and anti-apoptosis in several cell types, and an inducer of cancer stem cells; its critical roles in tumorigenesis are based on its oncogenic, mitogenic, proinflammatory, and pro-angiogenic actions. This review provides an update of the pathological effects of leptin signaling with special emphasis on potential molecular mechanisms and therapeutic targeting, which could potentially be used in future clinical settings. In addition, leptin-induced angiogenic ability and molecular mechanisms in HCC are discussed. The stringent binding affinity of leptin and its receptor Ob-R, as well as the highly upregulated expression of both leptin and Ob-R in cancer cells compared to normal cells, makes leptin an ideal drug target for the prevention and treatment of HCC, especially in obese patients.

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“…Importantly, epidemiological data has established a link between leptin over-expression and high risk of CRC 21 . Moreover, the promotion function of leptin on growth and migration of CRC has been elucidated 22–25 . In consistent, we found that MPS-1 was correlated with circulating leptin level in CRC patients, especially in obese cases, but not in non-obese cases.…”

Section: Discussionmentioning

confidence: 99%

Metallopanstimulin-1 (MPS-1) mediates the promotion effect of leptin on colorectal cancer through activation of JNK/c-Jun signaling pathway

Cao¹,

Luo²,

Qin³

et al. 2019

Cell Death Dis

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Obesity is a major epigenetic cause for colorectal cancer (CRC). Leptin is implicated in obesity-associated CRC, but the underlying mechanism remains unclear. The current study identified over-expression of metallopanstimulin-1 (MPS-1) in CRC patients through microarray and histological analysis, especially in obese CRC patients. MPS-1 was correlated with advanced tumor stage, suggesting its association with CRC progression. In addition, MPS-1 over-expression was associated with poor overall survival (OS) in obese CRC patients, but not in their non-obese counterparts, suggesting its potential as a prognostic marker of obese CRC patients. MPS-1 expression was positively associated with circulating leptin levels in CRC patients, especially in obese cases. Functional experiments demonstrated that MPS-1 silencing inhibited tumor proliferation and colony formation, and induced apoptosis of CRC cells in vitro. Converse results were obtained from the experiments with MPS-1 over-expression. Mechanistically, MPS-1 executed its action through induction of c-Jun N-terminal kinase (JNK)/c-Jun pathway. Moreover, the promotion effect of MPS-1 on CRC progression was modulated by leptin. In vivo studies demonstrated that MPS-1 silencing suppressed tumor growth of CRC via inhibiting JNK/c-Jun signaling. Collectively, this study indicates that MPS-1 promotes leptin-induced CRC via activating JNK/c-Jun pathway. MPS-1 might represent a potent candidate for the treatment and prognostic prediction of obesity-associated CRC.

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Oncogenic role and therapeutic target of leptin signaling in colorectal cancer

Abstract: Stringent binding affinity of leptin/Ob-R and overexpression of leptin/Ob-R and their targets in cancer cells make it a unique drug target for prevention and treatment of CRC, particularly in obesity colorectal patients.

Cited by 16 publications

References 146 publications

The prognostic and therapeutic role of hormones in colorectal cancer: a review

The prognostic and therapeutic role of hormones in colorectal cancer: a review

Leptin signaling molecular actions and drug target in hepatocellular carcinoma

Metallopanstimulin-1 (MPS-1) mediates the promotion effect of leptin on colorectal cancer through activation of JNK/c-Jun signaling pathway

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