scholarly journals RAS Subcellular Localization Inversely Regulates Thyroid Tumor Growth and Dissemination

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2588
Author(s):  
Yaiza García-Ibáñez ◽  
Garcilaso Riesco-Eizaguirre ◽  
Pilar Santisteban ◽  
Berta Casar ◽  
Piero Crespo
Keyword(s):  
Subcellular Localization ◽  
Tumor Growth ◽  
Specific Capacity ◽  
Thyroid Tumor ◽  
Membrane Microdomains ◽  
Clinical Samples ◽  
Thyroid Tumors ◽  
Thyroid Cells ◽  
Metastasis Model ◽  
Plasma Membrane Microdomains

RAS mutations are the second most common genetic alteration in thyroid tumors. However, the extent to which they are associated with the most aggressive phenotypes is still controversial. Regarding their malignancy, the majority of RAS mutant tumors are classified as undetermined, which complicates their clinical management and can lead to undesired under- or overtreatment. Using the chick embryo spontaneous metastasis model, we herein demonstrate that the aggressiveness of HRAS-transformed thyroid cells, as determined by the ability to extravasate and metastasize at distant organs, is orchestrated by HRAS subcellular localization. Remarkably, aggressiveness inversely correlates with tumor size. In this respect, we also show that RAS site-specific capacity to regulate tumor growth and dissemination is dependent on VEGF-B secretion. Furthermore, we have identified the acyl protein thioesterase APT-1 as a determinant of thyroid tumor growth versus dissemination. We show that alterations in APT-1 expression levels can dramatically affect the behavior of thyroid tumors, based on its role as a regulator of HRAS sublocalization at distinct plasma membrane microdomains. In agreement, APT-1 emerges in thyroid cancer clinical samples as a prognostic factor. As such, APT-1 levels could serve as a biomarker that could help in the stratification of HRAS mutant thyroid tumors based on their aggressiveness.

scholarly journals Flotillin microdomains interact with the cortical cytoskeleton to control uropod formation and neutrophil recruitment

2010 ◽  
Vol 191 (4) ◽  
pp. 771-781 ◽  
Author(s):  
Alexander Ludwig ◽  
Grant P. Otto ◽  
Kirsi Riento ◽  
Emily Hams ◽  
Padraic G. Fallon ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Ex Vivo ◽  
Neutrophil Migration ◽  
Neutrophil Recruitment ◽  
Membrane Microdomains ◽  
Neutrophil Chemotaxis ◽  
Myosin Iia ◽  
Plasma Membrane Microdomains ◽  
Cortical Cytoskeleton

We studied the function of plasma membrane microdomains defined by the proteins flotillin 1 and flotillin 2 in uropod formation and neutrophil chemotaxis. Flotillins become concentrated in the uropod of neutrophils after exposure to chemoattractants such as N-formyl-Met-Leu-Phe (fMLP). Here, we show that mice lacking flotillin 1 do not have flotillin microdomains, and that recruitment of neutrophils toward fMLP in vivo is reduced in these mice. Ex vivo, migration of neutrophils through a resistive matrix is reduced in the absence of flotillin microdomains, but the machinery required for sensing chemoattractant functions normally. Flotillin microdomains specifically associate with myosin IIa, and spectrins. Both uropod formation and myosin IIa activity are compromised in flotillin 1 knockout neutrophils. We conclude that the association between flotillin microdomains and cortical cytoskeleton has important functions during neutrophil migration, in uropod formation, and in the regulation of myosin IIa.

scholarly journals Topography of plasma membrane microdomains and its consequences for mast cell signaling

2006 ◽  
Vol 36 (10) ◽  
pp. 2795-2806 ◽  
Author(s):  
Petr Heneberg ◽  
Pavel Lebduška ◽  
L'ubica Dráberová ◽  
Jan Korb ◽  
Petr Dráber
Keyword(s):  
Mast Cell ◽  
Plasma Membrane ◽  
Cell Signaling ◽  
Membrane Microdomains ◽  
Plasma Membrane Microdomains

Status and expression of thep16INK4 gene in human thyroid tumors and thyroid-tumor cell lines

1996 ◽  
Vol 67 (1) ◽  
pp. 29-34 ◽  
Author(s):  
Viola Calabr� ◽  
Maria Strazzullo ◽  
Girolama La Mantia ◽  
Monica Fedele ◽  
Christian Paulin ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Thyroid Tumor ◽  
Human Thyroid ◽  
Thyroid Tumors ◽  
Tumor Cell Lines

scholarly journals Yeast cell wall integrity sensors form specific plasma membrane microdomains important for signalling

2016 ◽  
Vol 18 (9) ◽  
pp. 1251-1267 ◽  
Author(s):  
Christian Kock ◽  
Henning Arlt ◽  
Christian Ungermann ◽  
Jürgen J. Heinisch
Keyword(s):  
Cell Wall ◽  
Plasma Membrane ◽  
Yeast Cell ◽  
Cell Wall Integrity ◽  
Yeast Cell Wall ◽  
Membrane Microdomains ◽  
Plasma Membrane Microdomains

scholarly journals DC-SIGN and Influenza Hemagglutinin Dynamics in Plasma Membrane Microdomains Are Markedly Different

2011 ◽  
Vol 100 (11) ◽  
pp. 2662-2670 ◽  
Author(s):  
Michelle S. Itano ◽  
Aaron K. Neumann ◽  
Ping Liu ◽  
Feng Zhang ◽  
Enrico Gratton ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Membrane Microdomains ◽  
Influenza Hemagglutinin ◽  
Plasma Membrane Microdomains

scholarly journals EGFR transactivates RON to drive oncogenic crosstalk

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Carolina Franco Nitta ◽  
Ellen W Green ◽  
Elton D Jhamba ◽  
Justine M Keth ◽  
Iraís Ortiz-Caraveo ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Single Particle Tracking ◽  
Membrane Microdomains ◽  
Oncogenic Signaling ◽  
Nanoscale Imaging ◽  
Resolution Imaging ◽  
Ligand Stimulation ◽  
Plasma Membrane Microdomains ◽  
Stimulation Of ◽  
Formation Of Complexes

Crosstalk between different receptor tyrosine kinases (RTKs) is thought to drive oncogenic signaling and allow therapeutic escape. EGFR and RON are two such RTKs from different subfamilies, which engage in crosstalk through unknown mechanisms. We combined high-resolution imaging with biochemical and mutational studies to ask how EGFR and RON communicate. EGF stimulation promotes EGFR-dependent phosphorylation of RON, but ligand stimulation of RON does not trigger EGFR phosphorylation – arguing that crosstalk is unidirectional. Nanoscale imaging reveals association of EGFR and RON in common plasma membrane microdomains. Two-color single particle tracking captured formation of complexes between RON and EGF-bound EGFR. Our results further show that RON is a substrate for EGFR kinase, and that transactivation of RON requires formation of a signaling competent EGFR dimer. These results support a role for direct EGFR/RON interactions in propagating crosstalk, such that EGF-stimulated EGFR phosphorylates RON to activate RON-directed signaling.

scholarly journals BCAT1 Activates PI3K/AKT/mTOR Pathway and Contributes to the Angiogenesis and Tumorigenicity of Gastric Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiong Shu ◽  
Pan-Pan Zhan ◽  
Li-Xin Sun ◽  
Long Yu ◽  
Jun Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Growth ◽  
Western Blotting ◽  
Mtor Pathway ◽  
Clinical Samples ◽  
Xenograft Models ◽  
Cell Phenotypes

BackgroundFocusing on antiangiogenesis may provide promising choices for treatment of gastric cancer (GC). This study aimed to investigate the mechanistic role of BCAT1 in the pathogenesis of GC, particularly in angiogenesis.MethodsBioinformatics and clinical samples analysis were used to investigate the expression and potential mechanism of BCAT1 in GC. BGC823 cells with BCAT1 overexpression or silencing were induced by lentiviral transduction. Cell phenotypes and angiogenesis were evaluated. The relevant proteins were quantized by Western blotting, immunohistochemistry, or immunofluorescence. Xenograft models were constructed to confirm the role of BCAT1 in vivo.ResultsBCAT1 was overexpressed in GC patients and associated with lower survival. BCAT1 expression was correlated with proliferation-, invasion-, or angiogenesis-related markers expression and pathways. Silencing BCAT1 expression suppressed cell viability, colony formation, cycle progression, invasion, and angiogenesis of BGC823 cells, as well as the tumor growth of xenograft models, whereas overexpressing BCAT1 had the opposite results both in vitro and in vivo. Bioinformatics analysis and Western blotting demonstrated that BCAT1 activated the PI3K/AKT/mTOR pathway. The addition of LY294002 reversed the tumor growth induced by BCAT1 overexpression, further verifying this mechanism.ConclusionBCAT1 might act as an oncogene by facilitating proliferation, invasion, and angiogenesis through activation of the PI3K/AKT/mTOR pathway. This finding could aid the optimization of antiangiogenesis strategies.

scholarly journals Ptimary thyroid lymphomas and other rare thyroid tumors

2003 ◽  
Vol 50 (3) ◽  
pp. 141-146 ◽  
Author(s):  
Aleksandar Diklic ◽  
Vladan Zivaljevic ◽  
Ivan Paunovic ◽  
Ksenija Krgovic ◽  
Rastko Zivic ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Residual Tumor ◽  
Hashimoto Thyroiditis ◽  
Local Relapse ◽  
Thyroid Tumor ◽  
Recurrent Nerve ◽  
Thyroid Tumors ◽  
Treatment Frequency ◽  
Recurrent Nerve Palsy

Primary thyroid lymphomas are rare. Surgery is seldom indicated. The aim of the study is to find out the main characteristics of primary thyroid lymphomas in our patients, indications for surgery and the possibility of treatment, frequency and characteristics of rare thyroid tumors. Method: retrospective study of 1044 patient operated for malignant thyroid tumor. Results: From 1995 to may 2003, we operated upon 15 patients with primary thyroid lymphomas, 2 men and 13 women mean age of 50.12 years (from 22 to 74 years), also one patient of age 69 with insular thyroid cancer. Reason for surgery was thyroid tumor in all, compressive disturbances in 9, among them 4 with asphyxia. Radical total thyroidectomy was performed in 4 (26.7%), whole in others some residual tumor tissue was could not be removed in spite of thyroidectomy in 3, hemithyroidectomy in 2, tumor debulking in 5 and only open biopsy was performed in one patient. There was no operative mortality, no postoperative hypocalcaemia and no recurrent nerve palsy. Histological type of tumor was Non-Hodgkin lymphoma in 13 patients, Hodgkin disease in 2 female patients of age 22 and 24. Hashimoto thyroiditis was present in 3 patients. After surgery, 13 patients were treated with chemotherapy, one patient died one month after the operation and one patient refused chemotherapy. Follow-up data are available for 9 patients and the mean follow-up period was 20 months (1-48months). Three patients died after a month, 2 and 3 years after surgery. Six patients are without local relapse. In one patient who refused chemotherapy, a year after thyroid surgery, resection of large intestine was performed because of lymphoma of the colon. Conclusion: Malignant thyroid lymphomas are rare. They present with rapidly growing thyroid tumor, compression and asphyxia. Surgery is only temporarily effective and it is necessary to start with chemo-radiotherapy as soon as possible. Rare forms of thyroid cancer have to be histological recognized in order to choose the best way of treatment.

Sign in / Sign up

Export Citation Format

Share Document