FAM46B inhibits cell proliferation and cell cycle progression in prostate cancer through ubiquitination of β-catenin

Tao, Liang; Ye, Xuxiao; Liu, Yuanyuan; Qiu, Xinkai; Li, Zuowei; Tian, Baohong; Yan, Dongming

doi:10.1038/s12276-018-0184-0

Cited by 23 publications

(21 citation statements)

References 37 publications

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“…FAM46A expression was increased in glioma patients and cisplatin-resistant gastric cancer cell lines and associated with pathological grade, overall survival and progressionfree survival of glioma patients [6,7]. FAM46B expression was decreased in prostate cancer patients and inhibited cell proliferation and cell cycle progression through ubiquitination of β-catenin [8]. Deletions of FAM46C have been found in a few cancers, including multiple myeloma [9], gastric cancer [10] and myeloma [11], and to be associated with a shorter overall survival.…”

Section: Introductionmentioning

confidence: 99%

FAM46C inhibits cell proliferation and cell cycle progression and promotes apoptosis through PTEN/AKT signaling pathway and is associated with chemosensitivity in prostate cancer

Kang

et al. 2020

Aging

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Family with sequence similarity 46 member C (FAM46C) is a non-canonical poly(A) polymerase that is associated with tumorigenesis. However, its role in prostate cancer development is not fully understood. Herein, we determined expression pattern of FAM46C in prostate cancer and further identified its effect on the tumorigenesis and chemosensitivity. FAM46C expression was decreased in prostate cancer tissues and cell lines compared with corresponding controls. FAM46C expression was significantly associated with the Gleason score, tumor size and overall survival. FAM46C knockdown in 22RV1 and DU145 cells significantly inhibited apoptosis and promoted cell proliferation and cell cycle progression as well as activation of AKT. FAM46C overexpression had an inverse effect in DU145 cells and inhibited tumor growth in vivo. FAM46C inhibited cell proliferation and cell cycle progression and induced apoptosis via the PTEN/AKT signaling pathway. FAM46C promoted PTEN expression through inhibiting PTEN ubiquitination. The prostate cancer cells and patient-derived xenograft (PDX) mice with high-FAM46C-expressing demonstrated an enhanced chemosensitivity to docetaxel. These findings suggest that FAM46C control cell proliferation, cell cycle and apoptosis through PTEN/AKT signaling pathway and is associated with chemosensitivity of prostate cancer. Modulation of their levels may offer a new approach for improving anti-tumor efficacy for chemotherapeutic agents in prostate cancer.

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Section: Introductionmentioning

confidence: 99%

FAM46C inhibits cell proliferation and cell cycle progression and promotes apoptosis through PTEN/AKT signaling pathway and is associated with chemosensitivity in prostate cancer

Kang

et al. 2020

Aging

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“…Other potential regulators of LDHA include β-catenin, 31 which has been proposed to regulate MYC 32 and cyclin G2, 22 among others. As we have shown MYC to be regulated by FAM46B, and our previous study reported that FAM46B inhibits cell proliferation and cell cycle progression in prostate cancer through ubiquitination of β-catenin, 7 it is probable that FAM46B may regulate LDHA expression via the β-catenin /MYC signaling in prostate cancer. LDHA has been known to be involved throughout oncogenesis 33 particularly due to the increased energy needs of cancer cells.…”

Section: Discussionmentioning

confidence: 67%

“…6 FAM46B has been shown to reduce prostate tumor growth in an in vivo model through ubiquitination of β-catenin. 7 FAM46C has been found to have tumor-suppressing functions in multiple myeloma 8,9 as well as hepatocellular carcinoma. [10][11][12] Finally, FAM46D is a proposed cancer immunotherapy target.…”

Section: Introductionmentioning

confidence: 99%

<p>FAM46B Promotes Apoptosis and Inhibits Glycolysis of Prostate Cancer Through Inhibition of the MYC-LDHA Axis</p>

Tao

Yan

et al. 2020

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Increased dependence on glycolysis is a known element of cancer. This study was designed to examine critical glycolysis components including transcription factor MYC and its downstream target lactate dehydrogenase A (LDHA), potential upstream regulators of glycolysis such as family with sequence similarity 46 member B (FAM46B), and the impact of the abundance of these proteins on apoptosis and glycolysis in prostate cancer. Materials and Methods: A total of 70 primary prostate cancer patient samples were compared to normal tissues for FAM46B and LDHA expression and the corresponding patients' survival was monitored for 60 months. Prostate cancer cell lines were employed for protein expression manipulation, glucose uptake and LDH assays, and apoptosis measurements. A xenograft mouse model was used to quantify the role of FAM46B and LDHA on tumor growth in vivo. Results: FAM46B expression was reduced in prostate tumor tissue compared to normal tissue and prostate cancer patients who expressed low amounts of FAM46B had shortened average lifespans compared to those who expressed higher amounts of FAM46B (p=0.008). FAM46B overexpression reduced glucose uptake, decreased LDH activity, and induced apoptosis in prostate cancer cell lines while FAM46B shRNA increased MYC levels in a non-malignant prostate cell line (P69). Conversely, forced expression of LDHA in LNCaP cells produced an increase in glycolysis markers with a corresponding decrease in apoptosis. FAM46B-overexpressing xenografts had starkly blunted growth which was restored with cooverexpression of LDHA. Conclusion: FAM46B plays a central role in regulating glycolysis and apoptosis in prostate cancer and operates through the regulation of LDHA via MYC. FAM46B's keystone status in prostate cancer makes it a potential, robust biomarker for prostate cancer prognosis and a promising therapeutic target.

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“…34 In addition, β-catenin involved in the regulation of cell growth, cell cycle, and apoptosis. 35 Moreover, inhibition of β-catenin in cancer cells could suppress the cell cycle distribution via downregulating the expressions of Cyclin D1 and c-Myc. 35 Our data indicated that PTX had no effects on the expressions of βcatenin, c-Myc, and Cyclin D1 in SKOV3/PTX cells, whereas TET or combination treatment significantly downregulated the expressions of β-catenin, c-Myc and cyclin D1 in SKOV3/PTX cells, indicating that TET enhanced anti-tumor effect of PTX in SKOV3/PTX cells via inhibition the β-catenin/c-Myc/Cyclin D1 signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

<p>Tetrandrine Reverses Paclitaxel Resistance in Human Ovarian Cancer via Inducing Apoptosis, Cell Cycle Arrest Through β-Catenin Pathway</p>

Luo¹,

Hou²

2020

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Background: Paclitaxel (PTX) resistance is a great obstacle for the treatment of ovarian cancer. A previous study indicated that tetrandrine (TET) could induce the apoptosis of ovarian cancer cells. This study aimed to explore the effect of TET in combination with PTX on PTX resistance in ovarian cancer cells. Materials and Methods: CCK-8 assay, flow cytometry and wound healing assays were used to detect the proliferation, apoptosis and migration of PTX-resistant SKOV3 cells (SKOV3/PTX). The expressions of Bax, Bcl-2, cleaved caspase 3, β-catenin, c-Myc, cyclin D1 and p21 in SKOV3/PTX cells were detected with Western blot. In vivo animal study was performed finally. Results: In this study, the inhibitory effects of PTX on the proliferation and migration of SKOV3/PTX cells were markedly enhanced by TET. In addition, PTX-induced apoptosis in SKOV3/PTX cells was significantly enhanced by the treatment of TET via upregulating the levels of Bax and cleaved caspase 3, and downregulating the expression of Bcl-2. Moreover, combination of TET and PTX obviously induced cell cycle arrest in SKOV3/ PTX cells via increasing the level of p21 and decreasing the levels of c-Myc and Cyclin D1. Meanwhile, combination of TET with PTX significantly decreased the expression of βcatenin in SKOV3/PTX cells. In vivo experiments further confirmed that TET enhanced the anti-tumor effect of PTX in SKOV3/PTX xenograft model. Conclusion: We found that TET could enhance the sensitivity of SKOV3/PTX cells to PTX via inhibiting the β-catenin/c-Myc/Cyclin D1 signaling pathway. Therefore, PTX combined with TET might be considered as a potential approach for the treatment of PTX-resistant ovarian cancer.

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FAM46B inhibits cell proliferation and cell cycle progression in prostate cancer through ubiquitination of β-catenin

Cited by 23 publications

References 37 publications

FAM46C inhibits cell proliferation and cell cycle progression and promotes apoptosis through PTEN/AKT signaling pathway and is associated with chemosensitivity in prostate cancer

FAM46C inhibits cell proliferation and cell cycle progression and promotes apoptosis through PTEN/AKT signaling pathway and is associated with chemosensitivity in prostate cancer

<p>FAM46B Promotes Apoptosis and Inhibits Glycolysis of Prostate Cancer Through Inhibition of the MYC-LDHA Axis</p>

<p>Tetrandrine Reverses Paclitaxel Resistance in Human Ovarian Cancer via Inducing Apoptosis, Cell Cycle Arrest Through β-Catenin Pathway</p>

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