Kisspeptin/KISS1R System in Breast Cancer

Cvetković, Donna; Babwah, Andy V.; Bhattacharya, Moshmi

doi:10.7150/jca.7626

Cited by 43 publications

(33 citation statements)

References 95 publications

(155 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Activation of this G-coupled protein receptor by its canonical ligand, kisspeptin (metastin), has been shown to inhibit tumor cell migration and invasion in several cancers including RCC [48, 49]. Recently, a pro-invasive role has been proposed for KISS1R in breast cancer [50]. Data generated in this study additionally supports an invasive role for KISS1R in ccRCC.…”

Section: Resultssupporting

confidence: 68%

Functional genomics identifies novel genes essential for clear cell renal cell carcinoma tumor cell proliferation and migration

et al. 2014

View full text Add to dashboard Cite

Currently there is a lack of targeted therapies that lead to long-term attenuation or regression of disease in patients with advanced clear cell renal cell carcinoma (ccRCC). Our group has implemented a high-throughput genetic analysis coupled with a high-throughput proliferative screen in order to investigate the genetic contributions of a large cohort of overexpressed genes at the functional level in an effort to better understand factors involved in tumor initiation and progression.Patient gene array analysis identified transcripts that are consistently elevated in patient ccRCC as compared to matched normal renal tissues. This was followed by a high-throughput lentivirus screen, independently targeting 195 overexpressed transcripts identified in the gene array in four ccRCC cell lines. This revealed 31 ‘hits’ that contribute to ccRCC cell proliferation.Many of the hits identified are not only presented in the context of ccRCC for the first time, but several have not been previously linked to cancer. We further characterize the function of a group of hits in tumor cell invasion. Taken together these findings reveal pathways that may be critical in ccRCC tumorigenicity, and identifies novel candidate factors that could serve as targets for therapeutic intervention or diagnostic/prognostic biomarkers for patients with advanced ccRCC.

show abstract

Section: Resultssupporting

confidence: 68%

Functional genomics identifies novel genes essential for clear cell renal cell carcinoma tumor cell proliferation and migration

et al. 2014

View full text Add to dashboard Cite

show abstract

“…In vitro and in vivo downregulation of KISS1 in triple-negative breast cancer cells can also take part in the IL30-driven prometastatic program, although contrasting data on the metastasis suppression function of KISS1-derived peptides/KISS1R axis have been reported in breast cancer (39).…”

Section: Discussionmentioning

confidence: 99%

Interleukin-30 Promotes Breast Cancer Growth and Progression

et al. 2016

View full text Add to dashboard Cite

The inflammatory tissue microenvironment that promotes the development of breast cancer is not fully understood. Here we report a role for elevated IL30 in supporting the breast cancer cell viability and invasive migration. IL30 was absent in normal mammary ducts, ductules, and acini of histologically normal breast and scanty in the few stromal infiltrating leukocytes. In contrast, IL30 was expressed frequently in breast cancer specimens where it was associated with triple-negative and HER2 þ molecular subtypes. In stromal leukocytes found in primary tumors or tumor-draining lymph nodes, which included mainly CD14 þ monocytes, CD68 þ macrophages, and

show abstract

“…KISS1 encodes for Kisspeptin, which is a peptide ligand for G protein-coupled receptor KISS1R. KISS1 exhibits anti-metastatic effects in numerous human cancers, including melanoma, thyroid, ovarian, bladder, gastric, esophageal, pancreatic, lung, and pituitary cancers [83] [84]. Clinically, reduced KISS1 expression is associated with poor prognosis in cancer patients.…”

Section: Metastasis Regulators Impact Oxidative Metabolismmentioning

confidence: 99%

The Warburg effect in tumor progression: Mitochondrial oxidative metabolism as an anti-metastasis mechanism

2015

View full text Add to dashboard Cite

Compared to normal cells, cancer cells strongly upregulate glucose uptake and glycolysis to give rise to increased yield of intermediate glycolytic metabolites and the end product pyruvate. Moreover, glycolysis is uncoupled from the mitochondrial tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS) in cancer cells. Consequently, the majority of glycolysis-derived pyruvate is diverted to lactate fermentation and kept away from mitochondrial oxidative metabolism. This metabolic phenotype is known as the Warburg effect. While it has become widely accepted that the glycolytic intermediates provide essential anabolic support for cell proliferation and tumor growth, it remains largely elusive whether and how the Warburg metabolic phenotype may play a role in tumor progression. We hereby review the cause and consequence of the restrained oxidative metabolism, in particular in tumor metastasis. Cells change or lose their extracellular matrix during the metastatic process. Inadequate/inappropriate matrix attachment generates reactive oxygen species (ROS) and causes a specific type of cell death, termed anoikis, in normal cells. Although anoikis is a barrier to metastasis, cancer cells have often acquired elevated threshold for anoikis and hence heightened metastatic potential. As ROS are inherent byproducts of oxidative metabolism, forced stimulation of glucose oxidation in cancer cells raises oxidative stress and restores cells’ sensitivity to anoikis. Therefore, by limiting the pyruvate flux into mitochondrial oxidative metabolism, the Warburg effect enables cancer cells to avoid excess ROS generation from mitochondrial respiration and thus gain increased anoikis resistance and survival advantage for metastasis. Consistent with this notion, pro-metastatic transcription factors HIF and Snail attenuate oxidative metabolism, whereas tumor suppressor p53 and metastasis suppressor KISS1 promote mitochondrial oxidation. Collectively, these findings reveal mitochondrial oxidative metabolism as a critical suppressor of metastasis and justify metabolic therapies for potential prevention/intervention of tumor metastasis.

show abstract

Kisspeptin/KISS1R System in Breast Cancer

Cited by 43 publications

References 95 publications

Functional genomics identifies novel genes essential for clear cell renal cell carcinoma tumor cell proliferation and migration

Functional genomics identifies novel genes essential for clear cell renal cell carcinoma tumor cell proliferation and migration

Interleukin-30 Promotes Breast Cancer Growth and Progression

The Warburg effect in tumor progression: Mitochondrial oxidative metabolism as an anti-metastasis mechanism

Contact Info

Product

Resources

About