Asset Details
Do you wish to reserve the book?
Transmembrane and coiled-coil domain family 3 (TMCC3) regulates breast cancer stem cell and AKT activation
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?
Transmembrane and coiled-coil domain family 3 (TMCC3) regulates breast cancer stem cell and AKT activation
Do you wish to request the book?
Transmembrane and coiled-coil domain family 3 (TMCC3) regulates breast cancer stem cell and AKT activation
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
Transmembrane and coiled-coil domain family 3 (TMCC3) regulates breast cancer stem cell and AKT activation
2021
Overview
Cancer stem cells (CSC) play a pivotal role in cancer metastasis and resistance to therapy. Previously, we compared the phosphoproteomes of breast cancer stem cells (BCSCs) enriched subpopulation and non-BCSCs sorted from breast cancer patient-derived xenograft (PDX), and identified a function unknown protein, transmembrane and coiled-coil domain family 3 (TMCC3) to be a potential enrichment marker for BCSCs. We demonstrated greater expression of TMCC3 in BCSCs than non-BCSCs and higher expression of TMCC3 in metastatic lymph nodes and lungs than in primary tumor of breast cancer PDXs. TMCC3 silencing suppressed mammosphere formation, ALDH activity and cell migration in vitro, along with reduced tumorigenicity and metastasis in vivo. Mechanistically, we found that AKT activation was reduced by TMCC3 silencing, but enhanced by TMCC3 overexpression. We further demonstrated that TMCC3 interacted directly with AKT through its 1-153 a.a. domain by cell-free biochemical assay in vitro and co-immunoprecipitation and interaction domain mapping assays in vivo. Based on domain truncation studies, we showed that the AKT-interacting domain of TMCC3 was essential for TMCC3-induced AKT activation, self-renewal, and metastasis. Clinically,
TMCC3
mRNA expression in 202 breast cancer specimens as determined by qRT-PCR assay showed that higher
TMCC3
expression correlated with poorer clinical outcome of breast cancer, including early-stage breast cancer. Multivariable analysis identified
TMCC3
expression as an independent risk factor for survival. These findings suggest that TMCC3 is crucial for maintenance of BCSCs features through AKT regulation, and TMCC3 expression has independent prognostic significance in breast cancer. Thus, TMCC3 may serve as a new target for therapy directed against CSCs.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/31
/ 13/51
/ 13/95
/ 14/63
/ 38/1
/ 64/60
/ 82/58
/ 96/1
/ Animals
/ Breast Neoplasms - metabolism
/ Breast Neoplasms - pathology
/ Female
/ Humans
/ Medicine
/ Membrane Proteins - genetics
/ Membrane Proteins - metabolism
/ Mice
/ Neoplastic Stem Cells - metabolism
/ Oncology
/ Proto-Oncogene Proteins c-akt - genetics
