A5085330220- Cancer Cells and Metastasis
- Cancer, Hypoxia, and Metabolism
- HER2/EGFR in Cancer Research
- Cancer Mechanisms and Therapy
- Growth Hormone and Insulin-like Growth Factors
- Barrier Structure and Function Studies
- Cancer Research and Treatments
- Cancer Genomics and Diagnostics
- Metabolism, Diabetes, and Cancer
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Cell Adhesion Molecules Research
- Ferroptosis and cancer prognosis
- Cancer, Lipids, and Metabolism
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Glycosylation and Glycoproteins Research
- Immune cells in cancer
- Bone health and treatments
- RNA modifications and cancer
- Radiomics and Machine Learning in Medical Imaging
- Radiopharmaceutical Chemistry and Applications
- Axon Guidance and Neuronal Signaling
- TGF-β signaling in diseases
- Neurological Disease Mechanisms and Treatments
- Developmental Biology and Gene Regulation
McGill University Health Centre
2010-2024
McGill University
2014-2024
Occupational Cancer Research Centre
2015-2020
Université Laval
2005-2010
Hôtel-Dieu de Québec
2009
Centre hospitalier universitaire de Québec
2005
Neutrophils are phenotypically heterogeneous and exert either anti- or pro-metastatic functions. We show that cancer-cell-derived G-CSF is necessary, but not sufficient, to mobilize immature low-density neutrophils (iLDNs) promote liver metastasis. In contrast, mature high-density inhibit the formation of metastases. Transcriptomic metabolomic analyses high- reveal engagement numerous metabolic pathways specifically in neutrophils. iLDNs exhibit enhanced global bioenergetic capacity, through...
Abstract Introduction Breast cancer cells display preferences for specific metastatic sites including the bone, lung and liver. Metastasis is a complex process that relies, in part, on interactions between disseminated resident/infiltrating stromal constitute microenvironment. Distinct immune infiltrates can either impair or conversely, assist seeding, colonization growth of cells. Methods Using vivo selection approaches, we previously isolated 4T1-derived breast preferentially metastasize...
We previously identified claudin-2 as a functional mediator of breast cancer liver metastasis. now confirm that levels are elevated in metastases, but not skin compared to their matched primary tumors patients with cancer. Moreover, is specifically expressed liver-metastatic cells populations derived from bone or lung metastases. The increased tropism exhibited by claudin-2-expressing requires claudin-2-mediated interactions between and hepatocytes. Furthermore, the reduction expression...
Bone metastasis from breast and prostate carcinomas is facilitated by activation of bone-resorbing osteoclasts. Using proteomics approaches, we have identified peroxiredoxin-4 (PRDX4) as a cancer-secreted mediator osteoclastogenesis. We now report characterization L-plastin in the conditioned media (CM) MDA-MB-231 human cancer cells using immunoblotting mass spectrometry. The osteoclastogenic potential CM with siRNA-silenced was significantly reduced. detected cancer-derived exosomes,...
ShcA is an important mediator of ErbB2- and transforming growth factor β (TGF-β)-induced breast cancer cell migration, invasion, metastasis. We show that in the context reduced levels, bone morphogenetic protein (BMP) antagonist chordin-like 1 (Chrdl1) upregulated numerous cells following TGF-β stimulation. BMPs have emerged as modulators aggressiveness, we investigated ability Chrdl1 to block BMP-induced increases migration invasion. Breast cancer-derived conditioned medium containing...
Claudin-2 promotes breast cancer liver metastasis by enabling seeding and early cell survival. We now demonstrate that the PDZ-binding motif of is necessary for anchorage-independent growth cells required metastasis. Several PDZ domain-containing proteins were identified interact with in metastatic cells, including Afadin, Arhgap21, Pdlim2, Pdlim7, Rims2, Scrib, ZO-1. specifically examined role Afadin as a potential Claudin-2-interacting partner associates Claudin-2, an interaction requires...
Abstract Claudin-2 promotes breast cancer liver metastasis by enabling seeding and early cell survival. We now demonstrate that is functionally required for colorectal expression in primary cancers associated with poor overall metastasis-free have examined the role of Claudin-2, other claudin family members, as potential prognostic biomarkers desmoplastic replacement histopathological growth pattern metastases. Immunohistochemical analysis revealed higher levels type metastases when compared...
Abstract Colorectal cancer liver metastasis (CRCLM) has two major histopathological growth patterns: angiogenic desmoplastic and non-angiogenic replacement. The replacement lesions obtain their blood supply through vessel co-option, wherein the cells hijack pre-existing vessels of surrounding tissue. Consequentially, anti-angiogenic therapies are less efficacious in CRCLM patients with lesions. However, mechanisms which drive co-option unknown. Here, we show that Runt Related Transcription...
The management of hepatocellular carcinoma (HCC) is limited by the lack adequate screening biomarkers and chemotherapy. In response, there has been much interest in tumor metabolism as a therapeutic target. PCSK9 stimulates internalization LDL-receptor, decreases cholesterol uptake into hepatocytes affects liver regeneration. Thus, we investigated whether expression altered HCC, influencing its ability to harness metabolism. Thirty-nine patients undergoing partial hepatectomy or...
// Sébastien Tabariès 1, 2 , Matthew G. Annis Brian E. Hsu Christine Tam Paul Savage Morag Park 2, 3, 4 Peter M. Siegel 3 1 Goodman Cancer Research Centre, McGill University, Montréal, Québec, Canada, H3A 1A3 Department of Medicine, Biochemistry, Oncology, Correspondence to: Siegel, e-mail: peter.siegel@mcgill.ca Keywords: breast cancer, liver metastasis, claudins, Src family kinase, Lyn Received: January 26, 2015 Accepted: 31,...
The IGFI receptor promotes malignant progression and has been recognized as a target for cancer therapy. Clinical trials with anti-IGFIR antibodies provided evidence of therapeutic efficacy but exposed limitations due in part to effects on, the compensatory function of, insulin system. Here, we report on production, characterization, biologic activity novel, IGF-targeting protein (the IGF-Trap) comprising soluble form hIGFIR Fc portion hIgG1. IGF-Trap high affinity hIGFI hIGFII low insulin,...
Tight junctions (TJs) are large intercellular adhesion complexes that maintain cell polarity in normal epithelia and endothelia. Claudins critical components of TJs, forming homo- heteromeric interaction between adjacent cells, which have emerged as key functional modulators carcinogenesis metastasis. Numerous epithelial-derived cancers display altered claudin expression patterns, these aberrantly expressed claudins been shown to regulate cancer proliferation/growth, metabolism, metastasis...
Metabolic rewiring is essential for tumor growth and progression to metastatic disease, yet little known regarding how cancer cells modify their acquired metabolic programs in response different microenvironments. We have previously shown that liver-metastatic breast adopt an intrinsic program characterized by increased HIF-1α activity dependence on glycolysis. Here, we confirm vivo stable isotope tracing analysis (SITA) retain a glycolytic profile when grown as mammary tumors or liver...
Epithelial cells that lose attachment to the extracellular matrix undergo a specialized form of apoptosis called anoikis. Here, using large-scale RNA interference (RNAi) screening, we find KDM3A, histone H3 lysine 9 (H3K9) mono- and di-demethylase, plays pivotal role in anoikis induction. In attached breast epithelial cells, KDM3A expression is maintained at low levels by integrin signaling. Following detachment, signaling decreased resulting increased expression. RNAi-mediated knockdown...
Hox gene functions are intimately linked to correct developmental expression of the genes. The identification cis-acting regulatory sequences and their associated trans-acting factors constitutes a key step in deciphering mechanisms underlying positioning functional domain genes along anterior-posterior axis. We have identified DNA elements driving Hoxa5 regionalized mice, using 2.1-kb mesodermal enhancer (MES) localized 3′ flanking as starting point. MES sequence comprises targeting limbs,...
Background The genomic organization of Hox clusters is fundamental for the precise spatio-temporal regulation and function each gene, hence correct embryo patterning. Multiple overlapping transcriptional units exist at Hoxa5 locus reflecting complexity clustering: a major form 1.8 kb corresponding to two characterized exons gene polyadenylated RNA species 5.0, 9.5 11.0 kb. This intricacy raises question involvement larger transcripts in regulation. Methodology/Principal Findings We have...