Suppression of PPN/MG61 attenuates Wnt/β-catenin signaling pathway and induces apoptosis in human lung cancer

Chen, Z; Li, J; Li, Q S; Fan, Juan; Dong, Xiaoming; Xu, Jun‐Pu; Wang, X M; Yang, Guowang; Yan, Ping; Wen, Guang-Ming; Zhang, Y T; Niu, Rungui; Nan, Peng; He, Jia; Zhou, Hai‐Meng

doi:10.1038/sj.onc.1211006

Cited by 23 publications

(26 citation statements)

References 28 publications

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“…In particular, the dissimilar cellular composition of tumor and non-tumor tissue may strongly influence the expression level of total tissues. In this regard, we did not find a general increase in the mRNA expression level of Porcupine in human NSCLC compared to normal lung tissues contrary to recent reports (21). This has been shown for a high number of NSCLC tissues in two study groups and for two analytical methods.…”

Section: Discussioncontrasting

confidence: 99%

“…In accordance with this observation, silencing Porcupine induced a diminished expression of ß-Catenin in NSCLC cells. This effect of Porcupine on the expression of ß-Catenin and the ß-Catenin-dependent (canonical) Wnt signaling pathway in NSCLC cells was shown recently (21). As human NSCLC cells express the canonical Wnt molecules Wnt2, Wnt3, Wnt7a and Wnt9a (46), it suggests the primary contribution of Porcupine to the canonical Wnt signaling in NSCLC.…”

Section: Discussionmentioning

confidence: 68%

“…Silencing the expression of Porcupine in selected NSCLC cell lines resulted in a strong down-regulation of ß-Catenin and its targeted gene products (cyclin D1, dishevelled, frizzled 7, survivin) as well as in a dramatically increased apoptotic cell death (21). These data suggest the contribution of Porcupine to the canonical Wnt signaling, and probably non-canonical Wnt signaling, in NSCLC development.…”

Section: Introductionmentioning

confidence: 73%

“…Porcupine has been suggested as a critical factor involved in the survival of NSCLC cells but not lung fibroblasts by attenuating the canonical Wnt pathway (21). Although we used the same NSCLC cell line (NCI-A549), transient silencing of Porcupine by siRNA did not affect the viability of the NSCLC cells.…”

Section: Discussionmentioning

confidence: 95%

“…It has been reported that the transcription of Porcupine is increased in the non-small cell lung carcinoma (NSCLC) (21), which composes about 80% of all lung malignancies (22). Silencing the expression of Porcupine in selected NSCLC cell lines resulted in a strong down-regulation of ß-Catenin and its targeted gene products (cyclin D1, dishevelled, frizzled 7, survivin) as well as in a dramatically increased apoptotic cell death (21).…”

Section: Introductionmentioning

confidence: 99%

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Porcupine expression is associated with the expression of S100P and other cancer-related molecules in non-small cell lung carcinoma

Bartling

Rehbein²,

Simm³

et al. 2010

Int J Oncol

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Abstract. The Ô-acyltransferase Porcupine contributes to secretion and function of Wnt signaling molecules, which stimulate the expression of various cancer-related genes. Porcupine is also involved in the Wnt-induced cell signaling via ß-Catenin in non-small cell lung carcinoma (NSCLC) cells. Herein, we report that the expression level of Porcupine in human NSCLC tissues (n=89) positively correlates with the expression of several genes coding for cancer-related molecules such as ß-Catenin, Hypoxia-inducible factor-1· and Jun B. However, the mRNA expression of Porcupine was not generally increased in NSCLC compared to normal lung tissues. In NSCLC tissues we also found a positive correlation between the expression level of Porcupine and the calcium-binding protein S100P, which contributes to initiation and invasion of cancer cells. Subsequent studies showed that the DNA hypomethylation with 5-aza-2'deoxycytidine increased the mRNA expression of S100P in NSCLC cells but did not alter that of Porcupine. Silencing the expression of Porcupine with small interfering (si)RNA reduced the expression of S100P in NSCLC cells, whereas silencing the expression of S100P with siRNA did not effect the level of Porcupine expression. In conclusion, besides DNA methylation processes, Porcupine might regulate the expression of some cancer-related molecules including S100P in human NSCLC.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Porcupine expression is associated with the expression of S100P and other cancer-related molecules in non-small cell lung carcinoma

Bartling

Rehbein²,

Simm³

et al. 2010

Int J Oncol

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Therapeutics against Cancer Stem Cells: Targeting the Root of Cancer

Smith¹

2013

Encyclopedia of Molecular Cell Biology and Molecular Medicine

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Porcn as a novel therapeutic target in cancer therapy: A review

Raeisi

Saberivand

Velaei

et al. 2022

Cell Biology International

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Wingless-related integration site (Wnt) signaling is one of the main oncogenic pathways in different malignancies. Therefore, targeting this pathway has been considered an exciting strategy in cancer treatment. Porcn is among the central enzymes in this pathway that has recently been considered for cancer-targeted therapy. As a membrane-bound O-acyltransferase, Porcn plays a critical role in wnt ligand palmitoylation and its subsequent secretion. In addition to Porcn's role in stem cell signaling and differentiation, recent findings have shown its role in developing and progressing colorectal, pancreatic, liver, head, and neck cancers. Developed small molecule inhibitors have also opened a promising window toward cancer treatment strategies. In this review, the structure and biological role of Porcn in different cancer-related signaling pathways and inhibitors used for inhibiting this enzyme are discussed.

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Suppression of PPN/MG61 attenuates Wnt/β-catenin signaling pathway and induces apoptosis in human lung cancer

Cited by 23 publications

References 28 publications

Porcupine expression is associated with the expression of S100P and other cancer-related molecules in non-small cell lung carcinoma

Porcupine expression is associated with the expression of S100P and other cancer-related molecules in non-small cell lung carcinoma

Therapeutics against Cancer Stem Cells: Targeting the Root of Cancer

Porcn as a novel therapeutic target in cancer therapy: A review

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