MTOR/4EBP1 signaling and MMR status in colorectal cancer: New correlations and arising perspectives

Zouki, Dionysia N.; Giannopoulou, Ioanna; Alexandrou, Paraskevi; Karatrasoglou, Eleni A.; Pilichos, Georgios; Stamopoulos, Konstantinos; Kanellis, Theodore; Roupou, Eirini; Saetta, Angelica A.; Thymara, Irene; Kavantzas, Nikolaos; Lazaris, Andreas C.

doi:10.1016/j.prp.2021.153655

Cited by 4 publications

(4 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with our findings, a study reported that mTOR was aberrantly activated in 73.8% of cases, and a high level of p-mTOR was an independent adverse prognostic indicator in CRC patients [43] . However, in other studies, mTOR activation was not significantly linked to the survival of CRC patients [ 42 , 44 ]. Therefore, more research may be required to fully understand the link between mTOR hyperactivation and CRC prognosis.…”

Section: Discussionmentioning

confidence: 84%

See 1 more Smart Citation

Development of novel DNAJB6-KIAA1522-p-mTOR three-protein prognostic prediction models for CRC

Jiang

Zhang

Zhu

et al. 2023

Translational Oncology

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 84%

“…Although overactivation of mTOR is correlated with a poor prognosis in most cancer types, the prognostic significance of mTOR activation in CRC is still controversial [ 41 , 42 ]. Our earlier data revealed that p-mTOR was a potential prognostic marker in CRC [20] .…”

Section: Discussionmentioning

confidence: 99%

Development of novel DNAJB6-KIAA1522-p-mTOR three-protein prognostic prediction models for CRC

Jiang

Zhang

Zhu

et al. 2023

Translational Oncology

View full text Add to dashboard Cite

“…Hypoxia in CRC has been shown to induce oxidative stress and ROS production, which play a pivotal role in the delicate balance between tumor cell survival and death, as well as in various aspects of tumor development, including cell proliferation, metastasis, cell cycle progression, and senescence [21][22][23][24] . Notably, ROS activates the PI3K/AKT/mTOR pathway, which contributes to the excessive proliferation of cancer cells 25,26 . AKT, also known as protein kinase B (PKB), is a serine/threonine kinase downstream of PI3K that regulates cellular responses to external stimuli and controls cell proliferation and survival through various intracellular signaling cascades [27][28][29] .…”

Section: Discussionmentioning

confidence: 99%

Identification of 8 candidate microsatellite instability loci in colorectal cancer and validation of the ACVR2A mechanism in the tumor progression

Wang,

Zhang,

Liu

et al. 2024

Sci Rep

View full text Add to dashboard Cite

This study probes the utility of biomarkers for microsatellite instability (MSI) detection and elucidates the molecular dynamics propelling colorectal cancer (CRC) progression. We synthesized a primer panel targeting 725 MSI loci, informed by The Cancer Genome Atlas (TCGA) and ancillary databases, to construct an amplicon library for next-generation sequencing (NGS). K-means clustering facilitated the distillation of 8 prime MSI loci, including activin A receptor type 2A (ACVR2A). Subsequently, we explored ACVR2A’s influence on CRC advancement through in vivo tumor experiments and hematoxylin–eosin (HE) staining. Transwell assays gauged ACVR2A’s role in CRC cell migration and invasion, while colony formation assays appraised cell proliferation. Western blotting illuminated the impact of ACVR2A suppression on CRC’s PI3K/AKT/mTOR pathway protein expressions under hypoxia. Additionally, ACVR2A’s influence on CRC-induced angiogenesis was quantified via angiogenesis assays. K-means clustering of NGS data pinpointed 32 MSI loci specific to tumor and DNA mismatch repair deficiency (dMMR) tissues. ACVR2A emerged as a pivotal biomarker, discerning MSI-H tissues with 90.97% sensitivity. A curated 8-loci set demonstrated 100% sensitivity and specificity for MSI-H detection in CRC. In vitro analyses corroborated ACVR2A’s critical role, revealing its suppression of CRC proliferation, migration, and invasion. Moreover, ACVR2A inhibition under CRC-induced hypoxia markedly escalated MMP3, CyclinA, CyclinD1, and HIF1α protein expressions, alongside angiogenesis, by triggering the PI3K/AKT/mTOR cascade. The 8-loci ensemble stands as the optimal marker for MSI-H identification in CRC. ACVR2A, a central element within this group, deters CRC progression, while its suppression amplifies PI3K/AKT/mTOR signaling and angiogenesis under hypoxic stress.

show abstract

“…[32] Meanwhile, studies on the relationship between mTOR/p-mTOR expression and gastric cancer, breast cancer, colorectal cancer, nasopharyngeal carcinoma, and urinary system tumors have shown that mTOR or p-mTOR may be considered promising markers for predicting aggressiveness and prognosis of cancer. [33][34][35][36][37] In NSCLC, dysregulation of Akt/ mTOR signaling pathway activity is one of the primary factors of carcinogenesis. mTOR promotes tumorigenesis and progression through activation of the downstream eIF4 complexes.…”

Section: Introductionmentioning

confidence: 99%

The clinicopathological and prognostic significance of mTOR and p-mTOR expression in patients with non-small cell lung cancer: A meta-analysis

et al. 2022

View full text Add to dashboard Cite

Background: The mammalian target of rapamycin (mTOR) has a crucial role in carcinogenesis, angiogenesis, cellular proliferation, and metastasis; however, its significance in non-small cell lung cancer (NSCLC) remains contentious. Consequently, this study aims to assess the clinicopathological and prognostic importance of mTOR/p-mTOR expression in NSCLC. Methods: Literature retrieval was undertaken by searching English databases PubMed, EMBASE, Web of Science, and Cochrane Library as well as Chinese databases CNKI, Wan Fang, and VIP for full-text publications that satisfied our eligibility criteria up to November 2021. STATA 12.0 was used to conduct statistical analysis (STATA Corporation, College Station, TX). Results: This meta-analysis includes a total of 4683 patients from 28 primary publications. mTOR/p-mTOR expression was associated with sex (OR = 0.608, 95% CI: 0.442–0.836), lymph node metastasis (OR = 2.084, 95% CI: 1.437–3.182), and CEA (OR = 1.584, 95% CI: 1.135–2.209), but not with age, histological type, depth of tumor invasion, distant metastasis, TNM stage, differentiation degree, tumor size, or smoking. In addition, the expression of mTOR/p-mTOR is related to shorter overall survival in NSCLC patients (HR = 1.415, 95% CI: 1.051–1.905). Conclusion: Positive mTOR/p-mTOR expression was substantially correlated with unfavorable conditions on the sex, lymph node metastases, and CEA levels. mTOR/p-mTOR may indicate a bad prognosis for NSCLC. The current findings must be confirmed and changed by other high-quality research employing a multivariate analysis on bigger sample size.

show abstract

MTOR/4EBP1 signaling and MMR status in colorectal cancer: New correlations and arising perspectives

Cited by 4 publications

References 29 publications

Development of novel DNAJB6-KIAA1522-p-mTOR three-protein prognostic prediction models for CRC

Development of novel DNAJB6-KIAA1522-p-mTOR three-protein prognostic prediction models for CRC

Identification of 8 candidate microsatellite instability loci in colorectal cancer and validation of the ACVR2A mechanism in the tumor progression

The clinicopathological and prognostic significance of mTOR and p-mTOR expression in patients with non-small cell lung cancer: A meta-analysis

Contact Info

Product

Resources

About