Asset Details
Do you wish to reserve the book?
Yorkie-Cactus (IκBα)-JNK axis promotes tumor growth and progression in Drosophila
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Yorkie-Cactus (IκBα)-JNK axis promotes tumor growth and progression in Drosophila
Do you wish to request the book?
Yorkie-Cactus (IκBα)-JNK axis promotes tumor growth and progression in Drosophila
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Yorkie-Cactus (IκBα)-JNK axis promotes tumor growth and progression in Drosophila
2021
Overview
Presence of inflammatory factors in the tumor microenvironment is well-documented yet their specific role in tumorigenesis is elusive. The core inflammatory pathways like the Toll-Like Receptor (TLR) and the Tumor Necrosis Factor (TNF) pathway are conserved in
Drosophila
. We induced GFP-marked epithelial tumors by expressing activated oncogenic forms of
Ras
V12
or Yorkie (
Yki
3SA
, mammalian YAP) in
scribble
deficient cells (
scrib
RNAi
, mammalian SCRIB) to study the role of inflammatory factors in tumorigenesis. Similar to
Ras
V12
scrib
RNAi
, we found that
Yki
3SA
scrib
RNAi
form invasive neoplastic lethal tumors that induce a systemic inflammatory response. We identified Cactus (Cact, mammalian IκBα), the negative regulator of TLR, as a key player in tumor growth. Cact accumulates in the cytoplasm in
Drosophila
tumor models, similar to squamous cell carcinoma in mice models and human patients where cytoplasmic IκBα favors oncogenic transformation. Further,
cact
is transcriptionally upregulated in tumors, and downregulation of Cact affects tumor growth. We investigated if TLR or TNF pathway affect tumor growth through activation of Jun N-terminal Kinase (JNK) pathway and its target Matrix Metalloprotease1 (MMP1). Genetically manipulating levels of TLR components or TNF receptors showed that Cact acts upstream of JNK signaling and regulates JNK via a non-canonical mechanism during tumorigenesis. Further, Hippo coactivator Yki transcriptionally regulates
cact
expression, and downregulation of Yki or Cact is sufficient to cause downregulation of JNK-mediated signaling that promotes tumorigenesis. Here, we report a link between Hippo, IκBα and JNK signaling that may induce inflammation and innate immune response in tumorigenesis.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 14/19
/ 38
/ 64/24
/ 82/80
/ 96/1
/ Animals
/ Cancer
/ Cell Proliferation - genetics
/ Cellular signal transduction
/ DNA-Binding Proteins - genetics
/ Drosophila Proteins - genetics
/ Insects
/ JNK Mitogen-Activated Protein Kinases - genetics
/ Medicine
/ NF-KappaB Inhibitor alpha - genetics
/ Oncology
/ Signal Transduction - genetics
/ Transcription, Genetic - genetics
/ Tumor necrosis factor receptors
/ Tumors
