17 research outputs found
Septin 9_i2 is downregulated in tumors, impairs cancer cell migration and alters subnuclear actin filaments
International audienceFunctions of septin cytoskeletal polymers in tumorigenesis are still poorly defined. Their role in the regulation of cytokinesis and cell migration were proposed to contribute to cancer associated aneuploidy and metastasis. Overexpression of Septin 9 (Sept9) promotes migration of cancer cell lines. SEPT9 mRNA and protein expression is increased in breast tumors compared to normal and peritumoral tissues and amplification of SEPT9 gene was positively correlated with breast tumor progression. However, the existence of multiple isoforms of Sept9 is a confounding factor in the analysis of Sept9 functions. In the present study, we analyze the protein expression of Sept9_i2, an uncharacterized isoform, in breast cancer cell lines and tumors and describe its specific impact on cancer cell migration and Sept9 cytoskeletal distribution. Collectively, our results showed that, contrary to Sept9_i1, Sept9_ i2 did not support cancer cell migration, and induced a loss of subnuclear actin filaments. These effects were dependent on Sept9_i2 specific N-terminal sequence. Sept9_i2 was strongly down-regulated in breast tumors compared to normal mammary tissues. Thus our data indicate that Sept9_i2 is a negative regulator of breast tumorigenesis. We propose that Sept9 tumorigenic properties depend on the balance between Sept9_i1 and Sept9_i2 expression levels
Surgical Lip Repositioning in Two Patients Undergoing Orthodontic Treatment, With Degree I Vertical Maxillary Excess and Short Hypermobile Upper Lip
Lip Repositioning Procedure to Correct Excessive Gingival Display: A Case Report of Identical Twins
NUPR1 protects liver from lipotoxic injury by improving the endoplasmic reticulum stress response
Non-alcoholic fatty liver (NAFL) and related syndromes affect one-third of the adult
population in industrialized and developing countries. Lifestyle and caloric oversupply
are the main causes of such array of disorders, but the molecular mechanisms
underlying their etiology remain elusive. Nuclear Protein 1 (NUPR1) expression increases
upon cell injury in all organs including liver. Recently, we reported NUPR1
actively participates in the activation of the Unfolded Protein Response (UPR). The
UPR typically maintains protein homeostasis, but downstream mediators of the pathway
regulate metabolic functions including lipid metabolism. As increases in UPR
and NUPR1 in obesity and liver disease have been well documented, the goal of this
study was to investigate the roles of NUPR1 in this context. To establish whether
NUPR1 is involved in these liver conditions we used patient-derived liver biopsies
and in vitro and in vivo NUPR1 loss of functions models. First, we analyzed NUPR1
expression in a cohort of morbidly obese patients (MOPs), with simple fatty liver
(NAFL) or more severe steatohepatitis (NASH). Next, we explored the metabolic
roles of NUPR1 in wild-type (Nupr1+/+) or Nupr1 knockout mice (Nupr1−/−) fed
with a high-fat diet (HFD) for 15 weeks. Immunohistochemical and mRNA analysis
revealed NUPR1 expression is inversely correlated to hepatic steatosis progression.
Mechanistically, we found NUPR1 participates in the activation of PPAR-α signaling
via UPR. As PPAR-α signaling is controlled by UPR, collectively, these findings
suggest a novel function for NUPR1 in protecting liver from metabolic distress by
controlling lipid homeostasis, possibly through the UPR