A‐kinase interacting protein 1 (AKIP1) associates with advanced overall disease condition, tumor properties, and unfavorable prognosis in hepatocellular carcinoma patients

Fang, Tao; Lu, Qicheng

doi:10.1002/jcla.23213

Cited by 5 publications

(13 citation statements)

References 19 publications

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“…Recent studies have confirmed AKIP1 as a potential prognostic marker in several solid cancers 9,17,19 . For instance, CRC patients with positive tumor AKIP1 expression obviously have poorer OS rates when compare with those with negative tumor AKIP1 expression 19 .…”

Section: Discussionmentioning

confidence: 95%

“…In addition, AKIP1 expression is elevated in tumor tissue compared with paired adjacent tissue, and tumor AKIP1 expression is positively correlated with pathological differentiation, tumor size, lymph node metastasis, TNM stages, and abnormal CEA level in NSCLC patients 9 . Furthermore, tumor AKIP1 high expression has been illustrated to be correlated with higher performance status score, larger tumor size, barcelona clinic liver cancer (BCLC) stage B (vs stage A), increased alpha‐fetoprotein level and higher carbohydrate antigen 199 level in hepatocellular carcinoma patients 17 . However, to the best of our knowledge, the clinical value of AKIP1 in PTC patients has not yet been elucidated.…”

Section: Discussionmentioning

confidence: 97%

“…In breast cancer, overexpression of tumor AKIP1 is related to shorter OS and recurrence‐free survival in those patients 6 . In hepatocellular carcinoma, tumor AKIP1 high expression is related to worse OS, and it also is an independent predictive factor for shorter OS 17 . In line with these published studies, we found that according to classification of AKIP1 high/low expression, tumor AKIP1 high expression was correlated with poor DFS; according to classification of AKIP1 low/high+/high++/high+++ expression, increased grade of AKIP1 expression was also correlated with worse DFS, interestingly, higher tumor AKIP1 expression could predict independently poor DFS in PTC patients, which might be explained that: (a) AKIP1 could accelerate various cell signaling factors (such as CXCL1, NF‐κB and PKA) and multiple carcinogenic pathways (such as Slug‐induced EMT and Wnt/β‐catenin signaling pathway) to facilitate cell growth and metastasis, thereby participated in tumor development and led to worse prognosis in PTC patients 6,14‐16 .…”

Section: Discussionmentioning

confidence: 99%

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A‐kinase interacting protein 1 as a potential biomarker of advanced tumor features and increased recurrence risk in papillary thyroid carcinoma patients

Zhang¹,

Tao

Ke³

et al. 2020

Clinical Laboratory Analysis

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Background This study aimed to detect the expression of A‐kinase interacting protein 1 (AKIP1) and explore its correlation with clinicopathological features and clinical outcomes in papillary thyroid carcinoma (PTC) patients. Methods A total of 245 PTC patients treated by lobectomy or thyroidectomy were analyzed in this retrospective study. AKIP1 expression in tumor and adjacent tissue (from Specimen Room of our hospital) was detected by immunohistochemical (IHC) assay and then categorized as four grades: AKIP1 low (IHC score ≤3), high+ (IHC score 4‐6), high++ (IHC score 7‐9), and high+++ (IHC score 10‐12). Results A‐kinase interacting protein 1 low, high+, high++, and high+++ expression was 101 (41.2%), 101 (41.2%), 32 (13.1%), and 11 (4.5%) in tumor tissues, while was 173 (70.6%), 61 (24.9%), 9 (3.7%), and 2 (0.8%) in adjacent tissues. Further comparison analysis showed increased grade of AKIP1 expression in tumor tissues compared to adjacent tissue. Meanwhile, increased grade of tumor AKIP1 expression was correlated with larger tumor size, extrathyroidal invasion, increased pT stage, and higher pTNM stage. For prognosis, increased grade of tumor AKIP1 expression was correlated with shorter disease‐free survival (DFS), while was not correlated with overall survival (OS). Forward stepwise multivariate Cox's regression revealed that higher tumor AKIP1 was an independent factor predicting worse DFS, but not OS. Conclusion AKIP1 is upregulated in tumor tissue, and increased tumor AKIP1 expression correlates with advanced tumor features and increased recurrence risk in PTC patients, which suggest that AKIP1 severs as a potential marker for effective supervision of PTC progression.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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A‐kinase interacting protein 1 as a potential biomarker of advanced tumor features and increased recurrence risk in papillary thyroid carcinoma patients

Zhang¹,

Tao

Ke³

et al. 2020

Clinical Laboratory Analysis

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“…Most importantly, AKIP1 is also a promising oncology-related factor in recent studies. For instance, AKIP1 is upregulated in several cancers, and it also correlates with more deteriorative tumor features and survival profiles in these cancer patients, which suggests that it participates in the progression of many cancers (15)(16)(17)(18)(19). Above all, there is also correlation between AKIP1 and gastric cancer, which elucidates that it is involved in tumor progression through the modulation of Slug-induced epithelial-mesenchymal transition, which then enhances growth and metastasis of the tumor (20).…”

Section: Introductionmentioning

confidence: 90%

A-Kinase Interacting Protein 1 Promotes Cell Invasion and Stemness via Activating HIF-1α and β-Catenin Signaling Pathways in Gastric Cancer Under Hypoxia Condition

Luo

2022

Front. Oncol.

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BackgroundA-Kinase interacting protein 1 (AKIP1) relates to gastric cancer growth, metastasis, and prognosis, while its regulation on gastric cancer invasion and stemness under hypoxia microenvironment is not reported. Therefore, this study aimed to explore this topic to uncover AKIP1’s role in gastric cancer under hypoxia.MethodsGastric cancer cell lines AGS and MKN45 were cultured under hypoxia condition, then transfected with AKIP1 or negative control (NC) overexpression plasmid or AKIP1 or NC knockdown plasmid. Furthermore, rescue experiments were conducted by transfecting HIF-1α or β-catenin overexpression plasmid, combined with AKIP1 or NC knockdown plasmid. Afterward, cell invasion, CD133+ cell proportion, sphere number/1,000 cells, and HIF-1α and β-catenin pathways were measured.ResultsThe invasive cell count, CD133+ cell proportion, and sphere number/1,000 cells were enhanced in both AGS cells and MKN45 cells under hypoxia, and AKIP1 expression was also elevated. AKIP1 knockdown inhibited cell invasion, CD133+ cell proportion, sphere number/1,000 cells, HIF-1α, vascular endothelial growth factor (VEGF), β-catenin, and calcium-binding protein (CBP) expressions in AGS cells and MKN45 cells under hypoxia, while AKIP1 overexpression presented with the opposite effect. Then, in rescue experiments, HIF-1α overexpression and β-catenin overexpression both promoted cell invasion, CD133+ cell proportion, and sphere number/1,000 cells, which also attenuated the effect of AKIP1 knockdown on these functions in AGS cells and MKN45 cells.ConclusionAKIP1 promotes cell invasion and stemness via activating HIF-1α and β-catenin signaling pathways in gastric cancer under hypoxia condition.

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“…Additionally, it regulates the effect of the cAMP-dependent protein kinase signaling pathway on the NF-kappa-B activation cascade ( Gao et al, 2008 ; Gao et al, 2010 ). It is also related to the liver and endometrial cancer ( Zhang et al, 2018 ; Fang and Lu, 2020 ) and their prognosis. The metastatic lymph node 51 (CASC3, MLN51) protein is a required component of the spliceosome ( Zhang et al, 2017b ) which is responsible for pre-mRNA splicing in the cells.…”

Section: Methodsmentioning

confidence: 99%

Cell-Penetrating Peptides Predicted From CASC3, AKIP1, and AHRR Proteins

et al. 2021

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Peptides can be used as research tools and for diagnostic or therapeutic applications. Peptides, alongside small molecules and antibodies, are used and are gaining further interest as protein-protein interaction (PPI) modulators. Peptides have high target specificity and high affinity, but, unlike small molecule modulators, they are not able to cross the cell membranes to reach their intracellular targets. To overcome this limitation, the special property of the cell-penetrating peptides (CPPs) could benefit their cause. CPPs are a class of peptides that can enter the cells and with them also deliver the attached cargoes. Today, with the advancement of in silico prediction tools and the availability of protein databases, designing new and multifunctional peptides that are able to reach intracellular targets and inhibit certain cellular processes in a very specific manner is reachable. Although there are several efficient CPP sequences already known, the discovery of new CPPs is crucial for the development of efficient delivery methods for both biotechnological and therapeutic applications. In this work, we chose 10 human nuclear proteins from which we predicted new potential CPP sequences by using three different CPP predictors: cell-penetrating peptide prediction tool, CellPPD, and SkipCPP-Pred. From each protein, one predicted CPP sequence was synthesized and its internalization into cells was assessed. Out of the tested sequences, three peptides displayed features characteristic to CPPs. These peptides and also the predicted peptide sequences could be used to design and modify new CPPs. In this work, we show that we can use protein sequences as input for generating new peptides with cell internalization properties. Three new CPPs, AHRR8-24, CASC3251-264, and AKIP127-37, can be further used for the delivery of other cargoes or designed into multifunctional peptides with capability of internalizing cells.

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A‐kinase interacting protein 1 (AKIP1) associates with advanced overall disease condition, tumor properties, and unfavorable prognosis in hepatocellular carcinoma patients

Cited by 5 publications

References 19 publications

A‐kinase interacting protein 1 as a potential biomarker of advanced tumor features and increased recurrence risk in papillary thyroid carcinoma patients

A‐kinase interacting protein 1 as a potential biomarker of advanced tumor features and increased recurrence risk in papillary thyroid carcinoma patients

A-Kinase Interacting Protein 1 Promotes Cell Invasion and Stemness via Activating HIF-1α and β-Catenin Signaling Pathways in Gastric Cancer Under Hypoxia Condition

Cell-Penetrating Peptides Predicted From CASC3, AKIP1, and AHRR Proteins

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