Phosphatidylinositol glycan anchor biosynthesis, class X containing complex promotes cancer cell proliferation through suppression of EHD2 and ZIC1, putative tumor suppressors

Nakakido, Makoto; Takagi, Kenji; Chung, Suyoun; Ueda, Koji; Fujii, Risa; Kiyotani, Kazuma

doi:10.3892/ijo.2016.3607

Cited by 32 publications

(41 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several studies have demonstrated that downregulation of RCN1 in some cancer cells significantly suppresses cell proliferation . Our findings reinforce these observations that RCN1 deletion significantly suppresses PCa cell viability.…”

Section: Discussionsupporting

confidence: 91%

“…These observations suggest that RCN1 may not be directly correlated with the metastatic potential of PCa. High RCN1 and RCN2 expression has recently been associated with shorter recurrence‐free survival in breast cancer patients . Therefore, the contribution of RCN1 to carcinogenesis and cancer progression may be dependent on the cancer type.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Downregulation of reticulocalbin‐1 differentially facilitates apoptosis and necroptosis in human prostate cancer cells

et al. 2018

View full text Add to dashboard Cite

Reticulocalbin 1 (RCN1), an endoplasmic reticulum (ER)‐resident Ca2+‐binding protein, is dysregulated in cancers, but its pathophysiological roles are largely unclear. Here, we demonstrate that RCN1 is overexpressed in clinical prostate cancer (PCa) samples, associated with cyclin B, not cyclin D1 expression, compared to that of benign tissues in a Chinese Han population. Downregulation of endogenous RCN1 significantly suppresses PCa cell viability and arrests the cell cycles of DU145 and LNCaP cells at the S and G2/M phases, respectively. RCN1 depletion causes ER stress, which is evidenced by induction of GRP78, activation of PERK and phosphorylation of eIF2α in PCa cells. Remarkably, RCN1 loss triggers DU145 cell apoptosis in a caspase‐dependent manner but mainly causes necroptosis in LNCaP cells. An animal‐based analysis confirms that RCN1 depletion suppresses cell proliferation and promotes cell death. Further investigations reveal that RCN1 depletion leads to elevation of phosphatase and tensin homolog (PTEN) and inactivation of AKT in DU145 cells. Silencing of PTEN partially restores apoptotic cells upon RCN1 loss. In LNCaP cells, predominant activation of CaMKII is important for necroptosis in response to RCN1 depletion. Thus, RCN1 may promote cell survival and serve as a useful target for cancer therapy.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Downregulation of reticulocalbin‐1 differentially facilitates apoptosis and necroptosis in human prostate cancer cells

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Subtypes of ZICs were reported to play distinct roles in organism development [25], and were also reported to be closely associated with cancers. ZIC1 expression was shown to be increased in gastric cancers [26], and ZIC1 methylation was considered as a more promising biomarker of cervical cancers, head and neck squamous cell carcinomas and breast cancers [27][28][29]. Furthermore, Lu et al demonstrated that ZIC2 promoted hepatocellular tumor growth and metastasis [30].…”

Section: Discussionmentioning

confidence: 99%

Zinc finger of the cerebellum 5 promotes colorectal cancer cell proliferation and cell cycle progression through enhanced CDK1/CDC25c signaling

et al. 2021

View full text Add to dashboard Cite

Introduction: Colorectal cancer (CRC), mostly caused by external or environmental factors, is the third most common and lethal cancer worldwide. Although a large number of investigations have been carried out to reveal the evolution of CRC, the underlying mechanisms of CRC remain unclear. Material and methods: Expression of zinc finger of the cerebellum 5 (ZIC5) in CRC tissues and cell models was measured by qRT-PCR and IHC. Cell transfection was carried out for ZIC5 overexpression or knockdown. The MTT assay was applied to examine the capacity of glioma cell proliferation. Wound healing assay and tumor invasion assay were used to test the capacity of glioma cell migration and invasion respectively. Cell cycle analysis and western blot were used to verify the apoptosis rates of CRC cells upon ZIC5 overexpression or downregulation. A further tumor Xenograft study was used to examine the effects of ZIC5 on tumor malignancy in vivo. Results: Cell models using HCT116 and SW620 cells were established to study the ZIC5 function upon ZIC5 overexpression of knockdown. Consistently, we discovered that ZIC5 also significantly increased in Chinese CRC patients. In addition, ZIC5 promoted CRC cell proliferation through increasing the proportion of cells maintained in the S phase. ZIC5 overexpression facilitated the capacity of CRC cell migration and invasion. Inhibition of ZIC5 mitigated such malignant effects. Conclusions: Collectively, investigations of the ZIC5 in CRC provided a new insight into CRC diagnosis, treatment, prognosis and next-step translational therapeutic developments from bench to clinic.

show abstract

“…ZIC1 (Zinc finger of the cerebellum) is found to be highly suppressed via hypermethylation in colorectal cancer and is known to be a tumor suppressor Gan et al 97 . However, in breast cancer cases as Nakakido et al 98 show, the expression of ZIC1 is found to be regulated by the knockdown of PIGX as well as RCN1 (reticulocalbin 1) and (reticulocalbin 2) RCN2. Thus upregulation or overexpression of RCN2 negatively regulates ZIC1 for cancer proliferation.…”

Section: Dicationmentioning

confidence: 97%

“…However, in breast cancer cases as Nakakido et al 98 show, the expression of ZIC1 is found to be regulated by the knockdown of PIGX as well as RCN1 (reticulocalbin 1) and (reticulocalbin 2) RCN2. Thus upregulation or overexpression of RCN2 negatively regulates ZIC1 for cancer proliferation.…”

Section: Dicationmentioning

confidence: 97%

Revealing ETC-1922159 Affected Unknown 3<em><sup>rd</sup></em> order WNT10B-X-X Combinations, in Silico

Sinha¹

2017

Preprint

View full text Add to dashboard Cite

WNT10B belongs to the family of WNT proteins that are implicated in a range of phenomena that are affected by the Wnt signaling pathway. Recent studies have shown that WNT10B plays a role in colorectal cancer. WNTs have been found to directly affect the stemness of the tumor cells via regulation of ASCL2. Switching off the ASCL2 literally blocks the stemness process of the tumor cells and vice versa. Furthermore, recent findings suggest BVES to be highly suppressed in malignancies and in vitro deletions of BVES show higher Wnt signaling activity to induce stemness. WNT10B was found to be highly expressed in such cases. Often, in biology, we are faced with the problem of exploring relevant unknown biological hypotheses in the form of myriads of combination of factors that might be affecting the pathway under certain conditions. For example, WNT10B-ASCL2 is one such 2 nd order combination whose relation needs to be tested under the influence of recently developed porcupine-WNT inhibitor ETC-1922159. The inhibitor is known to suppress PORCN (porcupine) and thus inhibit a range of oncogenes known to be directly or indirectly affected by the Wnts. In a recent unpublished work in bioRxiv, Sinha 1 , we had the opportunity to rank these unknown biological hypotheses for down regulated genes at 2 nd order level after the drug was administered. The in silico observations showed that the combination of WNT10B-ASCL2 was assigned a relatively lower rank, thus validating the pipeline's efficacy with the confirmed wet lab experiment that indicate that both WNT10B and ASCL2 were down regulated after treatment in cancer cells. Here, we take one step further by in silico analysis of the 3 rd order combinations of WNT10B-X-X (X can be known or unknown factor), from a range of 100 randomly picked down regulated genes after ETC-1922159 treatment. The pipeline uses the density based HSIC (Hilbert Schmidt Information Criterion) sensitivity index with an rbf (radial basis function) kernel, which is known to be highly effective in sensitivity analysis. Various unknown/unexplored/untested 3 rd order biological hypotheses emerge some of which are confirmed in wet lab, while others need to be tested. The potential of such ranking is indispensable in the current era of search in a vast combinatorial forest. KEYWORDS -WNT pathway; porcupine inhibitor ETC-1922159; sensitivity analysis; colorectal cancer; unknown biological hypotheses; combinatorial search space; support vector ranking Conference, from 6-11 August 2017, held Significance WNT10B belongs to the family of WNT proteins that are implicated in a range of phenomena that are affected by the Wnt signaling pathway. Recent studies have shown that WNT10B plays a role in colorectal cancer. Often, we are faced with the problem of exploring relevant unknown biological hypotheses in the form of myriads of combination of factors that might be involved in the pathway. The current work reveals at in silico level, the 3rd order WNT10B associated combinations that might be affected by the admin...

show abstract

Phosphatidylinositol glycan anchor biosynthesis, class X containing complex promotes cancer cell proliferation through suppression of EHD2 and ZIC1, putative tumor suppressors

Cited by 32 publications

References 45 publications

Downregulation of reticulocalbin‐1 differentially facilitates apoptosis and necroptosis in human prostate cancer cells

Downregulation of reticulocalbin‐1 differentially facilitates apoptosis and necroptosis in human prostate cancer cells

Zinc finger of the cerebellum 5 promotes colorectal cancer cell proliferation and cell cycle progression through enhanced CDK1/CDC25c signaling

Revealing ETC-1922159 Affected Unknown 3<em><sup>rd</sup></em> order WNT10B-X-X Combinations, in Silico

Contact Info

Product

Resources

About