Leptin induces cell migration and invasion in a FAK-Src-dependent manner in breast cancer cells

Juárez-Cruz, Juan Carlos; Zuñiga-Eulogio, Miriam Daniela; Olea-Flores, Monserrat; Castañeda-Saucedo, Eduardo; Mendoza-Catalán, Miguel Ángel; Ortuño-Pineda, Carlos; Moreno‐Godínez, Ma. Elena; Villegas-Comonfort, Sócrates; Padilla‐Benavides, Teresita; Navarro-Tito, Napoleón

doi:10.1530/ec-19-0442

Cited by 47 publications

(52 citation statements)

References 60 publications

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“…Recently, Juárez-Cruz et al hypothesized that leptin promotes FAK and Src activation in breast cancer cells and induces cell migration, metalloproteases secretion (MMP2 and MMP9), and invasion. They suggested that leptin is associated with the establishment of a more aggressive phenotype of cancer cells that leads to local invasion and to the formation of metastases [73].…”

Section: Leptin and Bone Metastasismentioning

confidence: 99%

Leptin, Adiponectin, and Sam68 in Bone Metastasis from Breast Cancer

Maroni

2020

IJMS

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The most serious aspect of neoplastic disease is the spread of cancer cells to secondary sites. Skeletal metastases can escape detection long after treatment of the primary tumour and follow-up. Bone tissue is a breeding ground for many types of cancer cells, especially those derived from the breast, prostate, and lung. Despite advances in diagnosis and therapeutic strategies, bone metastases still have a profound impact on quality of life and survival and are often responsible for the fatal outcome of the disease. Bone and the bone marrow environment contain a wide variety of cells. No longer considered a passive filler, bone marrow adipocytes have emerged as critical contributors to cancer progression. Released by adipocytes, adipokines are soluble factors with hormone-like functions and are currently believed to affect tumour development. Src-associated in mitosis of 68 kDa (Sam68), originally discovered as a protein physically associated with and phosphorylated by c-Src during mitosis, is now recognised as an important RNA-binding protein linked to tumour onset and progression of disease. Sam68 also regulates splicing events and recent evidence reports that dysregulation of these events is a key step in neoplastic transformation and tumour progression. The present review reports recent findings on adipokines and Sam68 and their role in breast cancer progression and metastasis.

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Section: Leptin and Bone Metastasismentioning

confidence: 99%

Leptin, Adiponectin, and Sam68 in Bone Metastasis from Breast Cancer

Maroni

2020

IJMS

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“…Notably, compared to four individual prognosis-associated genes, the combined gene signature panel had better discrimination performance in COAD patients. LEP was reported to promote cancer cell migration and invasion (25,26). DLX2 was indicated to increase the risk of metastasis in prostate cancer patients with a high expression of Ki67 (27).…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis of Distant Metastasis-Associated Genes and Potential Drugs in Colon Adenocarcinoma

Lou

et al. 2020

Front. Oncol.

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Background: Most colon adenocarcinoma (COAD) patients die of distant metastasis, though there are some therapies for metastatic COAD. However, the genes exclusively expressed in metastatic COAD remain unclear. This study aims to identify prognosisrelated genes associated with distant metastasis and develop therapeutic strategies for COAD patients. Methods: Transcriptomic data from The Cancer Genome Atlas (TCGA; n = 514) cohort were analyzed as a discovery dataset. Next, the data from the GEPIA database and PROGgeneV2 database were used to validate our analysis. Key genes were identified based on the differential miRNA and mRNA expression with respect to M stage. The potential drugs targeting candidate differentially expressed genes (DEGs) were also investigated. Results: A total of 127 significantly DEGs in patients with distant metastasis compared with patients without distant metastasis were identified. Then, four prognosis-related genes (LEP, DLX2, CLSTN2, and REG3A) were selected based on clustering analysis and survival analysis. Finally, three compounds targeting the candidate DEGs, including ajmaline, TTNPB, and dydrogesterone, were predicted to be potential drugs for COAD. Conclusions: This study revealed that distant metastasis in COAD is associated with a specific group of genes, and three existing drugs may suppress the distant metastasis of COAD.

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“…Cruz et al [137] observed in in vitro models that leptin also promotes the activation of focal adhesion kinase, DOI: 10.1159/000507055 thus contributing to cell-cell adhesion weakening and increasing the secretion of metalloproteases (MMP-2 and MMP-9) required for ECM remodeling and cell migration in TNBC cell lines. Another study has demonstrated that free fatty acids added to co-cultures of breast cancer cells and adipocytes were transferred to cancer cells, driving fatty acid metabolism, resulting in increased proliferation and cell migration [138].…”

Section: Cancer-associated Adipocytesmentioning

confidence: 99%

“…Pathobiology 2020;87:[125][126][127][128][129][130][131][132][133][134][135][136][137][138][139][140][141][142] …”

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The Multifaceted Nature of Tumor Microenvironment in Breast Carcinomas

et al. 2020

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Heterogeneity in breast carcinomas can be appreciated at various levels, from morphology to molecular alterations, and there are well-known genotypic-phenotypic correlations. Clinical decision-making is strictly focused on the evaluation of tumor cells and is based on the assessment of hormone receptors and of the HER2 status, by means of a combination of immunohistochemical and in situ hybridization techniques. The tumor microenvironment (TME) also shows a multifaceted nature stemming from the different actors populating the intratumoral and the peritumoral stroma of breast carcinomas. Of note, we have now evidence that tumor-infiltrating lymphocytes (TILs) are clinically meaningful as their quantification in the intratumoral stroma strongly correlates with good prognosis, in particular in triple-negative and HER2-positive breast cancer patients. Nevertheless, TILs are just one of the many actors orchestrating the com-plexity of the TME, which is populated by immune and nonimmune cells (cancer-associated fibroblasts, cancer-associated adipocytes), as well as non-cellular components such as chemical inflammation mediators. In this review article we will overview the main features of the distinct cell compartments by discussing (i) the potential impact the TME may have on the prognostic stratification of breast cancers and (ii) the possible predictive value of some markers in the context of immunotherapy in light of the recent results of phase III studies in advanced and early triple-negative breast cancer patients.

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Leptin induces cell migration and invasion in a FAK-Src-dependent manner in breast cancer cells

Cited by 47 publications

References 60 publications

Leptin, Adiponectin, and Sam68 in Bone Metastasis from Breast Cancer

Leptin, Adiponectin, and Sam68 in Bone Metastasis from Breast Cancer

Integrated Analysis of Distant Metastasis-Associated Genes and Potential Drugs in Colon Adenocarcinoma

The Multifaceted Nature of Tumor Microenvironment in Breast Carcinomas

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