The MAP3K7-mTOR Axis Promotes the Proliferation and Malignancy of Hepatocellular Carcinoma Cells

Cheng, Jin‐Shiung; Tsai, Wei‐Lun; Liu, Pei‐Feng; Goan, Yih‐Gang; Lin, Chih‐Wen; Tseng, Ho-Hsing; Lee, Cheng-Hsin; Shu, Chih‐Wen

doi:10.3389/fonc.2019.00474

Cited by 21 publications

(29 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent evidence in the literature has indicated that MAP3K7 may also mediate AMPK-AKT-mTOR signaling, as MAP3K7/TAK1 inactivation is associated with AMPK activation and reduced p-mTOR levels in skeletal muscle [ 209 ]. However, MAP3K7 is reported to mediate mTOR signaling independently of AMPK in hepatocellular carcinoma, possibly via p38 activation [ 225 ].…”

Section: Genetic Aberrations In the Pi3k-akt-mtor Pathway In Prostmentioning

confidence: 99%

The PI3K-AKT-mTOR Pathway and Prostate Cancer: At the Crossroads of AR, MAPK, and WNT Signaling

Shorning

Dass

Smalley

et al. 2020

IJMS

359

251

View full text Add to dashboard Cite

Oncogenic activation of the phosphatidylinositol-3-kinase (PI3K), protein kinase B (PKB/AKT), and mammalian target of rapamycin (mTOR) pathway is a frequent event in prostate cancer that facilitates tumor formation, disease progression and therapeutic resistance. Recent discoveries indicate that the complex crosstalk between the PI3K-AKT-mTOR pathway and multiple interacting cell signaling cascades can further promote prostate cancer progression and influence the sensitivity of prostate cancer cells to PI3K-AKT-mTOR-targeted therapies being explored in the clinic, as well as standard treatment approaches such as androgen-deprivation therapy (ADT). However, the full extent of the PI3K-AKT-mTOR signaling network during prostate tumorigenesis, invasive progression and disease recurrence remains to be determined. In this review, we outline the emerging diversity of the genetic alterations that lead to activated PI3K-AKT-mTOR signaling in prostate cancer, and discuss new mechanistic insights into the interplay between the PI3K-AKT-mTOR pathway and several key interacting oncogenic signaling cascades that can cooperate to facilitate prostate cancer growth and drug-resistance, specifically the androgen receptor (AR), mitogen-activated protein kinase (MAPK), and WNT signaling cascades. Ultimately, deepening our understanding of the broader PI3K-AKT-mTOR signaling network is crucial to aid patient stratification for PI3K-AKT-mTOR pathway-directed therapies, and to discover new therapeutic approaches for prostate cancer that improve patient outcome.

show abstract

Section: Genetic Aberrations In the Pi3k-akt-mtor Pathway In Prostmentioning

confidence: 99%

The PI3K-AKT-mTOR Pathway and Prostate Cancer: At the Crossroads of AR, MAPK, and WNT Signaling

Shorning

Dass

Smalley

et al. 2020

IJMS

359

251

View full text Add to dashboard Cite

show abstract

“…Three-dimensional cell culture was performed as previously described, with minor modi cations. 34 NanoCulture system was used for 3D cell culture (organogenix). First, 100 ul of medium was added to each well.…”

Section: Three-dimensional Culturementioning

confidence: 99%

Sofosbuvir-Upregulated Genes Facilitate The Development of Hepatocellular Carcinoma

Tsai

Cheng

Pei-feng

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Direct-acting antivirals (DAAs) have achieved a sustained virological response (SVR) rate of 95-99% in treating HCV. Several studies suggested that treatment with sofosbuvir (SOF) containing DAAs may be associated with increased risk of developing HCC. The aim of this study is to investigate the potential mechanisms of SOF on the development of HCC.Methods: This study used OR-6 (harboring full-length genotype 1b HCV) and Huh 7.5.1 cells to examine the effects of SOF on cell proliferation and migration in HCC cells. SOF-upregulated genes in OR-6 cells were inspected using next generation sequencing (NGS) and the clinical significance of these candidate genes was analyzed using The Cancer Genome Atlas (TCGA) database. siRNA-mediated knockdown of candidate genes and their influence on cell proliferation and migration were also examined.Results: SOF increased cell proliferation and cell migration in OR-6 and Huh7.5.1 cells in both two- and three-dimensional culture models. NGS identified several genes that were significantly upregulated by SOF in OR-6 cells. Among these genes, PHOSPHO2, KLHL23, TRIM39, TSNAX-DISC1 and RPP21 expression were significantly elevated in the tumor part compared with the non-tumor part of HCC in the TCGA database. PHOSPHO2 and RPP21 were found to be associated with overall survival of HCC patients in the TCGA database. Moreover, knockdown of PHOSPHO2-KLHL23, TSNAX-DISC1, TRIM39 and RPP21 ameliorated cell proliferation and migration increased by SOF in OR-6 and Huh 7.5.1 cells. Conclusion: SOF upregulated several genes that were associated with increased cell proliferation and migration and the development of HCC.

show abstract

“…For the wound healing assay, the cells were transfected with siRNA for 48 h in a T25 culture flask. The cells (1.5 × 10 5 /140 µL) were then plated in culture inserts (IBIDI, Inc., Planegg, Germany) for 16 h [22]. Afterward, the inserts were removed to allow cells to migrate for 4 h. The distance covered by moving cells from time 0 to 4 h was counted as migration distance.…”

Section: Analysis Of Cell Viability Migration and Invasionmentioning

confidence: 99%

Association of ATG4B and Phosphorylated ATG4B Proteins with Tumorigenesis and Prognosis in Oral Squamous Cell Carcinoma

Liu

Chen

Cheng

et al. 2019

Cancers

Self Cite

View full text Add to dashboard Cite

Oral squamous cell carcinoma (OSCC) is one of the major leading causes of cancer death worldwide due to the limited availability of biomarkers and therapeutic targets. Autophagy related protease 4B (ATG4B) is an essential protease for the autophagy machinery, and ATG4B phosphorylation at Ser383/392 increases its proteolytic activity. ATG4B expression and activation are crucial for cancer cell proliferation and invasion. However, the clinical relevance of ATG4B and phospho-Ser383/392-ATG4B for OSCC remains unknown, particularly in buccal mucosal SCC (BMSCC) and tongue SCC (TSCC). With a tissue microarray comprising specimens from 498 OSCC patients, including 179 BMSCC and 249 TSCC patients, we found that the protein levels of ATG4B and phospho-Ser383/392-ATG4B were elevated in the tumor tissues of BMSCC and TSCC compared with those in adjacent normal tissues. High protein levels of ATG4B were significantly associated with worse disease-specific survival (DSS) in OSCC patients, particularly in patients with tumors at advanced stages. In contrast, phospho-Ser383/392-ATG4B expression was correlated with poor disease-free survival (DFS) in TSCC patients. Moreover, ATG4B protein expression was positively correlated with phospho-Ser383/392-ATG4B expression in both BMSCC and TSCC. However, high coexpression levels of ATG4B and phospho-Ser383/392-ATG4B were associated with poor DFS only in TSCC patients, whereas they had no significant association with DSS in BMSCC and TSCC patients. In addition, silencing ATG4B with an antisense oligonucleotide (ASO) or small interfering RNA (siRNA) diminished cell proliferation of TW2.6 and SAS oral cancer cells. Further, knockdown of ATG4B reduced cell migration and invasion of oral cancer cells. Taken together, these findings suggest that ATG4B might be a biomarker for diagnosis/prognosis of OSCC and a potential therapeutic target for OSCC patients.

show abstract

The MAP3K7-mTOR Axis Promotes the Proliferation and Malignancy of Hepatocellular Carcinoma Cells

Cited by 21 publications

References 53 publications

The PI3K-AKT-mTOR Pathway and Prostate Cancer: At the Crossroads of AR, MAPK, and WNT Signaling

The PI3K-AKT-mTOR Pathway and Prostate Cancer: At the Crossroads of AR, MAPK, and WNT Signaling

Sofosbuvir-Upregulated Genes Facilitate The Development of Hepatocellular Carcinoma

Association of ATG4B and Phosphorylated ATG4B Proteins with Tumorigenesis and Prognosis in Oral Squamous Cell Carcinoma

Contact Info

Product

Resources

About