Par3 regulates invasion of pancreatic cancer cells via interaction with Tiam1

Guo, Xiaomao; Wang, Min; Zhao, Yan; Wang, Xin; Shen, Ming; Zhu, Feng; Shi, Changcheng; Xu, Meng; Xu, Li; Peng, Feng; Zhang, Hang; Feng, Yechen; Xie, Yu; Xu, Xiaodong; Jia, Wei Hua; He, Ruizhi; Jiang, Jianxin; Hu, Jun; Tian, Rui; Qin, Renyi

doi:10.1007/s10238-015-0365-2

Cited by 21 publications

(19 citation statements)

References 22 publications

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“…Silencing of the expression and/or function of these proteins, either due to genetic alterations or epigenetic regulation, modulates claudin expression, and induces loss of polarity and EMT [8, 22, 53]. Interestingly, genetic modulation of claudin proteins in mice or cancer cells can similarly affect these signaling cascades, suggesting a feedback regulation.…”

Section: Introductionmentioning

confidence: 99%

Claudin proteins, outside-in signaling, and carcinogenesis

Singh¹,

Uppada

Dhawan³

2016

Pflugers Arch - Eur J Physiol

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Environment affects an individual’s development and disease risk which then suggest that the environmental cues must have ways of reaching to the cellular nuclei to orchestrate desired genetic changes. Polarized and differentiated epithelial cells join together by cell-cell adhesions to create a protective sheet which separates body’s internal milieu from its environment, albeit in highly regulated manner. Among these cell-cell adhesions, a key role of tight junction, the apical cell-cell adhesion, in maintaining epithelial cell polarity and differentiation is well recognized. Moreover, significant changes in expression and cellular distribution of claudin proteins, integral component of the tight junction, characterize pathophysiological changes including neoplastic growth and progression. Studies have further confirmed existence of complex claudin-based interactomes and demonstrated that changes in such protein partnering can influence barrier integrity and communication between a cell and its environment to produce undesired outcome. Cell signaling is the process by which cells respond to their environment to make dynamic decisions to live, grow and proliferate, or die. Thus, pivotal role of the deregulated tight junction structure/function in influencing cellular signaling cascades to alter cellular pheno-type can be envisaged, however, is not well understood. Needless to mention that advanced knowledge in this area can help improve therapeutic considerations and preventive measures. Here, we discuss potential role of the tight junction in the regulation of Boutside-in^ signaling to regulate cancer growth, with specific focus upon the claudin family of proteins.

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Section: Introductionmentioning

confidence: 99%

Claudin proteins, outside-in signaling, and carcinogenesis

Singh¹,

Uppada

Dhawan³

2016

Pflugers Arch - Eur J Physiol

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“…F2rl2 is a member of the protease‐activated receptor‐3 family and is involved in homeostasis, adhesion, proliferation, and migration (Fig. 6) (46, 47). Although we observed that both genes were hypomethylated at this specific site, we noticed a 76‐fold difference in the extent of underexpression, with Iqgap2 >378‐ and F2rl2 >5‐fold underexpressed.…”

Section: Discussionmentioning

confidence: 99%

Altered methylation of specific DNA loci in the liver of Bhmt‐null mice results in repression of Iqgap2 and F2rl2 and is associated with development of preneoplastic foci

et al. 2017

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Folate B-dependent remethylation of homocysteine is important, but less is understood about the importance of the alternative betaine-dependent methylation pathway-catalyzed by betaine-homocysteine methyltransferase (BHMT)-for establishing and maintaining adequate DNA methylation across the genome. We studied C57Bl/6J (betaine-homocysteine methyltransferase)-null mice at age 4, 12, 24, and 52 wk ( = 8) and observed elevation of -adenosylhomocysteine concentrations and development of preneoplastic foci in the liver (increased placental glutathione-transferase and cytokeratin 8-18 activity; starting at 12 wk). At 4 wk, we identified 63 differentially methylated CpGs (DMCs; false discovery rate < 5%) proximal to 81 genes (across 14 chromosomes), of which 18 were differentially expressed. Of these DMCs, 52% were located in one 15.5-Mb locus on chromosome 13, which encompassed the gene and defined a potentially sensitive region with mostly decreased methylation. Analyzing Hybrid Mouse Diversity Panel data, which consisted of 100 inbred strains of mice, we identified 97 DMCs that were affected by genetic variation in the same region, with 7 overlapping those found in -null mice ( < 0.001). At all time points, we found a hypomethylated region mapping to (IQ motif-containing GTPase activating protein 2) and (proteinase-activated receptor-3), 2 genes that were also silenced and underexpressed, respectively.-Lupu, D. S., Orozco, L. D., Wang, Y., Cullen, J. M., Pellegrini, M., Zeisel, S. H. Altered methylation of specific DNA loci in the liver of -null mice results in repression of and and is associated with development of preneoplastic foci.

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“…In pancreatic tumor, glioblastoma, head and neck squamous cell carcinoma, and esophageal squamous cell carcinoma, PAR3 acts as tumor suppressor and is positively associated with overall survival rate of cancer patients. [3][4][5][6][7] However, in some other tumors, such as liver cancer, ovarian cancer, and renal clear cell carcinoma, PAR3 overexpression supports cancer cell proliferation and is associated with poor cancer prognosis. [8][9][10][11] All these evidences implicated the complex regulatory network of cell polarity and its interaction with oncogenic and tumor suppressor pathways.…”

Section: Discussionmentioning

confidence: 99%

“…3,4 Also, PAR3 controls tight junction assembly in pancreatic cells and absence of PAR3 is associated with poor prognosis of pancreatic cancer. 5 In addition, PAR3 reduction has also been frequently reported in esophageal squamous cell carcinoma, 6 head and neck squamous cell carcinoma, and primary glioblastoma tumors, 7 all of which suggest a tumor-suppressing function of PAR3. However, all the growing evidences implicated the oncogenic role of PAR3.…”

Section: Introductionmentioning

confidence: 98%

High expression of partitioning defective 3–like protein is associated with malignancy in colorectal cancer

Liu

Jiang

et al. 2017

Tumour Biol.

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Partitioning defective 3-like protein is a novel cell polarity protein. Recently, partitioning defective 3-like protein has been demonstrated with tumor-promoting function by disrupting tight junction, inhibiting tumor suppressor liver kinase B1, and maintaining mammary stem cells. For the first time, we studied partitioning defective 3-like protein expression in malignant colorectal cancer. We used immunohistochemistry scoring system to evaluate partitioning defective 3-like protein expression in 196 colorectal cancer tissues and 33 adjacent normal tissues. We found that colorectal cancer tissues had much stronger partitioning defective 3-like protein immunoreactivity than normal tissues, and colorectal cancer patients with positive partitioning defective 3-like protein expression were characterized with higher cancer stages, metastasis, poor tumor differentiation, larger tumor size, as well as high levels of colorectal cancer markers carcinoembryonic antigen and cancer antigen 19-9. Besides, partitioning defective 3-like protein overexpression was independently predictive of lower survival rate in colorectal cancer patients, even after adjusting the influence of cofactors. Moreover, we also found that partitioning defective 3-like protein was associated with rapid growing colorectal cancer, while knockdown of partitioning defective 3-like protein expression largely inhibited cancer cell proliferation. Our study provided the first evidence that partitioning defective 3-like protein was overexpressed in colorectal cancer and associated with disease malignancy. Also, partitioning defective 3-like protein may serve as a promising prognostic marker and a potential therapeutic target for colorectal cancer treatment. Further study is necessary to understand the regulatory mechanism of partitioning defective 3-like protein in colorectal cancer and the feasibility of its application in clinic.

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Par3 regulates invasion of pancreatic cancer cells via interaction with Tiam1

Cited by 21 publications

References 22 publications

Claudin proteins, outside-in signaling, and carcinogenesis

Claudin proteins, outside-in signaling, and carcinogenesis

Altered methylation of specific DNA loci in the liver of Bhmt‐null mice results in repression of Iqgap2 and F2rl2 and is associated with development of preneoplastic foci

High expression of partitioning defective 3–like protein is associated with malignancy in colorectal cancer

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