Project description:To characterize pancreatic neuroendocrine tumor at protein level, we performed mass spectromery-based proteome analysis using clinical FFPE tissue samples.

2024-07-10 | PXD034571 | Pride

Engrailed-1 Promotes Pancreatic Cancer Metastasis

Project description:Engrailed-1 Promotes Pancreatic Cancer Metastasis

| PRJNA951660 | ENA

RABL6A promotes G1-S phase progression and pancreatic neuroendocrine tumor cell proliferation in an Rb1-dependent manner

Project description:Mechanisms of neuroendocrine tumor (NET) proliferation are poorly understood and therapies that effectively control NET progression and metastatic disease are limited. We found amplification of a putative oncogene, RABL6A, in primary human pancreatic NETs (PNETs) that correlated with high level RABL6A protein expression. Consistent with those results, stable silencing of RABL6A in cultured BON-1 PNET cells revealed that it is essential for their proliferation and survival. Cells lacking RABL6A predominantly arrested in G1 phase with a moderate mitotic block. Pathway analysis of microarray data suggested activation of the p53 and retinoblastoma (Rb1) tumor suppressor pathways in the arrested cells. Specific inactivation of p53 had no effect on the RABL6A knockdown phenotype, indicating RABL6A functions independent of p53 in this setting. By comparison, Rb1 inactivation restored G1 to S phase progression in RABL6A knockdown cells although it was insufficient to override the mitotic arrest and cell death caused by RABL6A loss. Thus, RABL6A promotes G1 progression in PNET cells by inactivating Rb1, an established suppressor of PNET proliferation and development. This work identifies RABL6A as a new negative regulator of Rb1 that is essential for PNET proliferation and survival. We suggest RABL6A is a new potential biomarker and target for anticancer therapy in PNET patients. Total RNA obtained from human BON-1 PNET cells with RABL6A shRNA knockdown compared to BON-1 cells expressing control vector.

2014-07-01 | E-GEOD-53778 | biostudies-arrayexpress

Pericyte-fibroblast transition promotes tumor growth and metastasis

Project description:Vascular pericytes, an important cellular component, in the tumor microenvironment, are often associated with tumor vasculatures and their functions in cancer invasion and metastasis are poorly understood. Here we show that PDGF-BB induces pericyte fibroblast transition (designated as PFT), which significantly contributes to tumor invasion and metastasis. Gain- and loss-of-function experiments demonstrate that the PDGF-BB-PDGFRÎ² signaling promotes PFT in vitro and in in vivo tumors. Genome-wide expression analysis indicates that PDGF-BB-activated pericytes acquire mesenchymal progenitor features. Pharmacological inhibition and genetic deletion of PDGFRÎ² ablate the PDGF-BB-induced PFT. Genetic tracing of pericytes with two independent mouse strains, i.e., TN-AP-CreERT2:R26R-tdTomato and NG2:R26R-tdTomato, shows that PFT cells gains stromal fibroblast and myofibroblast markers in tumors. Importantly, co-implantation of PFT cells with less-invasive tumor cells in mice markedly promotes tumor dissemination and invasion, leading to an increased number of circulating tumor cells (CTCs) and metastasis. Our findings reveal a novel mechanism of vascular pericytes in PDGF-BB-promoted cancer invasion and metastasis by inducing PFT and thus targeting PFT may offer a new treatment option of cancer metastasis. Pericytes were isolated and treated with PDGF-BB or control for 1 or 5 days

2016-08-24 | E-GEOD-85955 | biostudies-arrayexpress

Single-cell RNA-sequencing of metastatic pancreatic neuroendocrine tumor

Project description:Single-cell RNA-sequencing of metastatic pancreatic neuroendocrine tumor

| PRJNA682637 | ENA

Methionine oxidation of PKM2 promotes pancreatic cancer metastasis

Project description:Methionine oxidation of PKM2 promotes pancreatic cancer metastasis

| PRJNA743050 | ENA