scholarly journals MAPK6-AKT signaling promotes tumor growth and resistance to mTOR kinase blockade

2021 ◽  
Vol 7 (46) ◽  
Author(s):  
Qinbo Cai ◽  
Wolong Zhou ◽  
Wei Wang ◽  
Bingning Dong ◽  
Dong Han ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Akt Signaling ◽  
Mtor Kinase

scholarly journals INPP4B promotes PI3Kα-dependent late endosome formation and Wnt/β-catenin signaling in breast cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Samuel J. Rodgers ◽  
Lisa M. Ooms ◽  
Viola M. J. Oorschot ◽  
Ralf B. Schittenhelm ◽  
Elizabeth V. Nguyen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Akt Signaling ◽  
Late Endosome ◽  
Breast Cancers ◽  
Lysosomal Degradation ◽  
Late Endosomes ◽  
Mrna And Protein Expression

AbstractINPP4B suppresses PI3K/AKT signaling by converting PI(3,4)P2 to PI(3)P and INPP4B inactivation is common in triple-negative breast cancer. Paradoxically, INPP4B is also a reported oncogene in other cancers. How these opposing INPP4B roles relate to PI3K regulation is unclear. We report PIK3CA-mutant ER+ breast cancers exhibit increased INPP4B mRNA and protein expression and INPP4B increased the proliferation and tumor growth of PIK3CA-mutant ER+ breast cancer cells, despite suppression of AKT signaling. We used integrated proteomics, transcriptomics and imaging to demonstrate INPP4B localized to late endosomes via interaction with Rab7, which increased endosomal PI3Kα-dependent PI(3,4)P2 to PI(3)P conversion, late endosome/lysosome number and cargo trafficking, resulting in enhanced GSK3β lysosomal degradation and activation of Wnt/β-catenin signaling. Mechanistically, Wnt inhibition or depletion of the PI(3)P-effector, Hrs, reduced INPP4B-mediated cell proliferation and tumor growth. Therefore, INPP4B facilitates PI3Kα crosstalk with Wnt signaling in ER+ breast cancer via PI(3,4)P2 to PI(3)P conversion on late endosomes, suggesting these tumors may be targeted with combined PI3K and Wnt/β-catenin therapies.

scholarly journals Biallelic loss of FAM46C triggers tumor growth with concomitant activation of Akt signaling in multiple myeloma cells

2020 ◽  
Vol 111 (5) ◽  
pp. 1663-1675 ◽  
Author(s):  
Jo Kanasugi ◽  
Ichiro Hanamura ◽  
Akinobu Ota ◽  
Sivasundaram Karnan ◽  
Vu Quang Lam ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Tumor Growth ◽  
Akt Signaling ◽  
Myeloma Cells

scholarly journals MicroRNA-519a promotes tumor growth by targeting PTEN/PI3K/AKT signaling in hepatocellular carcinoma

2015 ◽  
Vol 48 (3) ◽  
pp. 965-974 ◽  
Author(s):  
KANGSHENG TU ◽  
ZHIKUI LIU ◽  
BOWEN YAO ◽  
SHAOSHAN HAN ◽  
WEI YANG
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Akt Signaling

scholarly journals SLC3A2 is upregulated in human osteosarcoma and promotes tumor growth through the PI3K/Akt signaling pathway

2017 ◽  
Vol 37 (5) ◽  
pp. 2575-2582 ◽  
Author(s):  
Bin Zhu ◽  
Dongdong Cheng ◽  
Lei Hou ◽  
Shumin Zhou ◽  
Tao Ying ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Human Osteosarcoma

Selenadiazole Derivatives Inhibit Angiogenesis-Mediated Human Breast Tumor Growth by Suppressing the VEGFR2-Mediated ERK and AKT Signaling Pathways

2018 ◽  
Vol 13 (11) ◽  
pp. 1447-1457 ◽  
Author(s):  
Haoqiang Lai ◽  
Xiaoyan Fu ◽  
Chengcheng Sang ◽  
Liyuan Hou ◽  
Pengju Feng ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Signaling Pathways ◽  
Breast Tumor ◽  
Akt Signaling ◽  
Human Breast ◽  
Human Breast Tumor

scholarly journals Loss of G-Protein Pathway Suppressor 2 Promotes Tumor Growth Through Activation of AKT Signaling

2021 ◽  
Vol 8 ◽  
Author(s):  
Stefanie Chan ◽  
Emma Smith ◽  
Yuan Gao ◽  
Julian Kwan ◽  
Benjamin C. Blum ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Tumor Growth ◽  
G Protein ◽  
Molecular Mechanisms ◽  
Akt Signaling ◽  
Proteomic Profiling ◽  
Potential Biomarker ◽  
Regulated Gene Expression

G Protein Suppressor 2 (GPS2) is a multifunctional protein that exerts important roles in inflammation and metabolism in adipose, liver, and immune cells. GPS2 has recently been identified as a significantly mutated gene in breast cancer and other malignancies and proposed to work as a putative tumor suppressor. However, molecular mechanisms by which GPS2 prevents cancer development and/or progression are largely unknown. Here, we have profiled the phenotypic changes induced by GPS2 depletion in MDA-MB-231 triple negative breast cancer cells and investigated the underlying molecular mechanisms. We found that GPS2-deleted MDA-MB-231 cells exhibited increased proliferative, migratory, and invasive properties in vitro, and conferred greater tumor burden in vivo in an orthotopic xenograft mouse model. Transcriptomic, proteomic and phospho-proteomic profiling of GPS2-deleted MBA-MB-231 revealed a network of altered signals that relate to cell growth and PI3K/AKT signaling. Overlay of GPS2-regulated gene expression with MDA-MB-231 cells modified to express constitutively active AKT showed significant overlap, suggesting that sustained AKT activation is associated with loss of GPS2. Accordingly, we demonstrate that the pro-oncogenic phenotypes associated with GPS2 deletion are rescued by pharmacological inhibition of AKT with MK2206. Collectively, these observations confirm a tumor suppressor role for GPS2 and reveal that loss of GPS2 promotes breast cancer cell proliferation and tumor growth through uncontrolled activation of AKT signaling. Moreover, our study points to GPS2 as a potential biomarker for a subclass of breast cancers that would be responsive to PI3K-class inhibitor drugs.

Sign in / Sign up

Export Citation Format

Share Document