Targeting PI3K/AKT pathway in triple-negative breast cancer

Delaloge, Suzette; DeForceville, Louise

doi:10.1016/s1470-2045(17)30514-4

Cited by 39 publications

(26 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was identified that the activation of this pathway was associated with enhanced cell growth and clinical outcome, and its overexpression correlated with a worse prognosis of tumor, which proposed it might be a therapeutic potential strategic point for BC. 34 , 35 Aforementioned evidence demonstrates that PI3K/AKT signaling may be involved in the action of CLEC3A knockdown inducing anti-proliferation and anti-metastasis potency of BC. In spite of this, limitation of the current work should be acknowledged.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of CLEC3A promotes tumor progression and poor prognosis in breast invasive ductal cancer

Ni¹,

Peng²,

Yang³

et al. 2018

OTT

View full text Add to dashboard Cite

IntroductionThe aim of this study was to evaluate the expression of C-type lectin domain family 3 member A (CLEC3A) and its clinical significance in breast invasive ductal cancer (IDC) as well as its effect on breast cancer (BC) cell proliferation and metastasis. In this study, the level of CLEC3A expression in The Cancer Genome Atlas (TCGA) datasets was analyzed.Materials and methodsClinical collected samples and BC cells were measured using quantitative reverse transcription polymerase chain reaction. Its correlations with patients’ clinicopathological characteristics were analyzed by Pearson’s chi-squared test. Overall survival (OS) analysis was performed by the Kaplan–Meier method and Cox’s proportional-hazards model. BC cell proliferation, migration, and invasion by CLEC3A knockdown were assessed using Cell Counting Kit-8 and colony formation assay, wound healing model and transwell assay, respectively, in BT474 cell line. Activities of survival factors and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling were measured by testing key molecules using Western blot assay.ResultsCLEC3A expression was markedly higher in breast IDC tissues than normal breast tissues or adjacent normal tissue. Patients with high CLEC3A expression related to higher lymph node and poorer OS of breast IDC. CLEC3A knockdown by siRNA could inhibit the BC cells BT474 proliferation, migration, and invasion, together with a decrease in expression of key proteins in survival factors and PI3K/AKT signaling pathway.ConclusionElevated CLEC3A expression may correlate with breast IDC metastatic potential and indicated a poor prognosis in breast IDC. CLEC3A knockdown inhibited BC cell growth and metastasis might be through suppressing PI3K/AKT signaling activity. These findings unravel that CLEC3A is a promising therapeutic target for BC in the future.

show abstract

Section: Discussionmentioning

confidence: 99%

Overexpression of CLEC3A promotes tumor progression and poor prognosis in breast invasive ductal cancer

Ni¹,

Peng²,

Yang³

et al. 2018

OTT

View full text Add to dashboard Cite

show abstract

“…Combination treatments attempt to overcome this problem by targeting several pathways simultaneously [4]. Thus, although VEGFR and EGFR inhibitors have failed to improve overall survival, they are still considered promising for combination therapies [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Targeting the non-canonical roles of PCNA modifies and increases the response to targeted anti-cancer therapy

et al. 2019

View full text Add to dashboard Cite

Receptor tyrosine kinases (RTKs), such as HER2 and/or EGFR are important therapeutic targets in multiple cancer cells. Low and/or short response to targeted therapies are often due to activation of compensatory signaling pathways, and therefore a combination of kinase inhibitors with other anti-cancer therapies have been proposed as promising strategies. PCNA is recently shown to have non-canonical cytosolic roles, and targeting PCNA with a cell-penetrating peptide containing the PCNA-interacting motif APIM is shown to mediate changes in central signaling pathways such as PI3K/Akt and MAPK, acting downstream of multiple RTKs. In this study, we show how targeting PCNA increased the anti-cancer activity of EGFR/ HER2/VEGFR inhibition in vitro as well as in vivo. The combination treatment resulted in reduced tumor load and increased the survival compared to either single agent treatments. The combination treatment affected multiple cellular signaling responses not seen by EGFR/HER2/VEGFR inhibition alone, and changes were seen in pathways determining protein degradation, ER-stress, apoptosis and autophagy. Our results suggest that targeting the non-canonical roles of PCNA in cellular signaling have the potential to improve targeted therapies.

show abstract

“…AKT is well established as the predominant PI3K effector in many cell types [ 5 ]. Many cancer genetic alterations deregulate cell signaling pathways and exert their oncogenic effects in part through the PI3K/AKT pathway [ 6 , 7 ]. Hence, there is a particularly intimate relationship between the activation of the AKT signaling pathway and tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

“…Hence, there is a particularly intimate relationship between the activation of the AKT signaling pathway and tumorigenesis. Activation of PI3K results in the phosphorylation of two key residues on AKT, i.e., Thr308 in the activation motif and Ser473 in a C-terminal hydrophobic motif [ 7 , 8 ]. AKT can translocate from the plasma membrane to intracellular compartments, including the cytoplasm and nucleus where it phosphorylates substrates [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

A cytoplasmic long noncoding RNA LINC00470 as a new AKT activator to mediate glioblastoma cell autophagy

et al. 2018

View full text Add to dashboard Cite

BackgroundDespite the overwhelming number of investigations on AKT, little is known about lncRNA on AKT regulation, especially in GBM cells.MethodsRNA-binding protein immunoprecipitation assay (RIP) and RNA pulldown were used to confirm the binding of LINC00470 and fused in sarcoma (FUS). Confocal imaging, co-immunoprecipitation (Co-IP) and GST pulldown assays were used to detect the interaction between FUS and AKT. EdU assay, CCK-8 assay, and intracranial xenograft assays were performed to demonstrate the effect of LINC00470 on the malignant phenotype of GBM cells. RT-qPCR and Western blotting were performed to test the effect of LINC00470 on AKT and pAKT.ResultsIn this study, we demonstrated that LINC00470 was a positive regulator for AKT activation in GBM. LINC00470 bound to FUS and AKT to form a ternary complex, anchoring FUS in the cytoplasm to increase AKT activity. Higher pAKT activated by LINC00470 inhibited ubiquitination of HK1, which affected glycolysis, and inhibited cell autophagy. Furthermore, higher LINC00470 expression was associated with GBM tumorigenesis and poor patient prognosis.ConclusionsOur findings revealed a noncanonical AKT activation signaling pathway, i.e., LINC00470 directly interacts with FUS, serving as an AKT activator to promote GBM progression. LINC00470 has an important referential significance to evaluate the prognosis of patients.Electronic supplementary materialThe online version of this article (10.1186/s13045-018-0619-z) contains supplementary material, which is available to authorized users.

show abstract

Targeting PI3K/AKT pathway in triple-negative breast cancer

Cited by 39 publications

References 7 publications

Overexpression of CLEC3A promotes tumor progression and poor prognosis in breast invasive ductal cancer

Overexpression of CLEC3A promotes tumor progression and poor prognosis in breast invasive ductal cancer

Targeting the non-canonical roles of PCNA modifies and increases the response to targeted anti-cancer therapy

A cytoplasmic long noncoding RNA LINC00470 as a new AKT activator to mediate glioblastoma cell autophagy

Contact Info

Product

Resources

About