Association of the Actin-Binding Protein Transgelin with Lymph Node Metastasis in Human Colorectal Cancer

Buckhaults, Phillip; Lee, Jeffrey R.; Xiong, Hairong; Farrell, Christopher L.; Podolsky, Robert H.; Schade, Robert R.; Dynan, William S.

doi:10.1593/neo.09542

Cited by 83 publications

(108 citation statements)

References 63 publications

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“…TMA used in the confirmatory studies represented 94 cases of eligible CRC specimens (14 node-negative, 22 node-positive) and was used for immunohistochemistry with anti-PRDX6 antibody. This TMA contained carcinoma samples in duplicate, with normal control colonic mucosa [16]. Immunostaining was assessed independently by a pathologist in a blinded manner.…”

Section: Tissue Samples and Assessment Of Crc Tissue Microarrays (Tmas)mentioning

confidence: 99%

Expression of PRDX6 Correlates with Migration and Invasiveness of Colorectal Cancer Cells

Huang

Hsieh

et al. 2018

Cell Physiol Biochem

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Background/Aims: Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer-related deaths worldwide. PRDXs are antioxidant enzymes that play an important role in cell differentiation, proliferation and apoptosis and have diverse functions in malignancy development. However, the mechanism of aberrant overexpression of PRDX6 in CRC remains unclear. Methods: Boyden chamber assay, flow cytometry and a lentiviral shRNA targeting PRDX6 and transient transfection with pCMV-6-PRDX6 plasmid were used to examine the role of PRDX6 in the proliferation capacity and invasiveness of CRC cells. Immunohistochemistry (IHC) with tissue array containing 40 paraffin- embedded CRC tissue specimens and Western blot assays were used to detect target proteins. Results: PRDX6 was significantly up-expressed in different comparisons of metastasis of colorectal adenomas in node-positive CRC (P = 0.03). In in vitro HCT-116, PRDX6 silencing markedly suppressed CRC cell migration and invasiveness while also inducing cell cycle arrest as well as the generation of reactive oxygen species (ROS); specific overexpression of PRDX6 had the opposite effect. Mechanistically, the PRDX6 inactivation displayed decreased levels of PRDX6, N-cadherin, β-catenin, Vimentin, Slug, Snail and Twist-1 through the activation of the PI3K/ AKT/p38/p50 pathways, but they were also significantly inhibited by PRDX6 transfectants. There was also increased transcriptional activation of dimethylation of histone H3 lysine 4 (H3K4me3) of PRDX6 promoter via the activation of the PI3K/Akt/NFkB pathways. Conclusion: Our findings demonstrated that PRDX6 expression plays a characteristic growth-promoting role in CRC metastasis. This study suggests that PRDX6 may serve as a biomarker of node-positive status and may have a role as an important endogenous regulator of cancer cell tumorigenicity in CRC. PRDX6 may also be an effective therapeutic target.

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Section: Tissue Samples and Assessment Of Crc Tissue Microarrays (Tmas)mentioning

confidence: 99%

Expression of PRDX6 Correlates with Migration and Invasiveness of Colorectal Cancer Cells

Huang

Hsieh

et al. 2018

Cell Physiol Biochem

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“…Following surgery, the 5-year survival rate of patients with early-stage colorectal cancer is >90%, however, the 5-year survival rate of advanced-stage patients is <10% (6). Although several genes associated with lymph node metastasis have been reported, the molecular mechanisms of early-stage metastasis in colorectal cancer remain unclear (7)(8)(9). Thus, the identification of bio-markers associated with lymph node metastasis of colorectal cancer will benefit clinical evaluation and future treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

Effects of autophagy regulation of tumor-associated macrophages on radiosensitivity of colorectal cancer cells

Shao

Zhu

Chen

et al. 2016

Molecular Medicine Reports

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Abstract. Tumor-associated macrophages (TAMs), a major component of the tumor microenvironment, are crucial to the processes of tumor growth, infiltration and metastasis, and contribute to drug resistance. The importance of TAMs in radiation resistance of colorectal cancer remains unclear. To investigate the effects of autophagy regulation of TAMs on the radiosensitivity of colorectal cancer cells, the current study induced TAM formation from THP-1 monocyte cells. Sequential treatment of THP-1 cells with PMA for 72 h and human recombinant interleukin-4 for 24 h was used to stimulate THP-1 differentiation to TAMs. Expression of the cell surface markers CD68, CD204 and CD206, and changes to cell morphology were used to confirm successful differentiation. The TAMs were stimulated to promote or inhibit autophagy during co-culture with LoVo colorectal adenocarcinoma cells. The cells were irradiated, with subsequent measurement of LoVo colony formation and apoptosis. Additionally, the expression of p53, Bcl-2, survivin and Smac proteins was assessed by western blotting. Monodansylcadaverin staining was used to analyze the presence of autophagic vacuoles in TAM, and western blot analysis was used to assess the expression of Beclin-1, LC3B I and II, ATG-3, -5 and -7. The results demonstrated TAM autophagy to be markedly altered by rapamycin and bafilomycin A1 treatment. Following co-culture with TAMs, the colony formation rate and survival fraction of LoVo cells were significantly higher than those in the control group (P<0.05). It was further demonstrated that the regulation of autophagy in TAMs was able to inhibit the colony formation of LoVo colorectal cancer cells. Upregulation of TAM autophagy using rapamycin exhibited more effective inhibition of LoVo colony formation than autophagy downregulation. Notably, apoptosis was significantly increased in LoVo cells when co-cultured with TAMs only, or with rapamycin-mediated autophagy upregulated TAMs, compared with LoVo cells cultured alone (P<0.01). Expression of Bcl-2, survivin and p53 were reduced in LoVo cells co-cultured with TAMs, compared with the control group (P<0.05), whereas Smac expression was increased in the co-culture groups (P<0.01). It was demonstrated that rapamycin-mediated autophagy stimulation in TAMs led to reduced expression levels of survivin and Bcl-2, however, Smac expression was increased. The upregulation of autophagy in TAMs inhibited proliferation and induced apoptosis in colon cancer cells, and altered the expression of radiosensitivity-associated proteins. This data indicated that the radiosensitivity of colorectal cancer cells is associated with autophagy of TAM, and that stimulating TAM autophagy may increase the radiosensitivity of colorectal cancer cells.

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“…Previous research by this group (56) revealed that activated AKT and c-jun NH2-terminal kinases promote the expression of transgelin in the cytoplasm and contribute to colorectal cancer progression. Additionally, it is revealed that transgelin was located in the cytoplasm and nucleus of colorectal cancer cells (57). Overexpression of transgelin in human colon cancer cells affects the expression of ~250 other transcripts and enhances the metastatic behavior (58).…”

Section: Nuclear Abps In Cancer Cellsmentioning

confidence: 99%

Functions of nuclear actin-binding proteins in human cancer (Review)

Yang

2017

Oncol Lett

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Abstract. Nuclear actin-binding proteins (ABPs) perform distinguishable functions compared with their cytoplasmic counterparts in extensive activities of living cells. In addition to the ability to regulate actin cytoskeleton dynamics, nuclear ABPs are associated with multiple nuclear biological processes, including chromatin remodeling, gene transcriptional regulation, DNA damage response, nucleocytoplasmic trafficking and nuclear structure maintenance. The nuclear translocation of ABPs is affected by numerous intracellular or extracellular stimuli, which may lead to developmental malformation, tumor initiation, tumor progression and metastasis. Abnormal expression of certain ABPs have been reported in different types of cancer. This review focuses on the newly identified roles of nuclear ABPs in the pathological processes associated with cancer.

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Association of the Actin-Binding Protein Transgelin with Lymph Node Metastasis in Human Colorectal Cancer

Cited by 83 publications

References 63 publications

Expression of PRDX6 Correlates with Migration and Invasiveness of Colorectal Cancer Cells

Expression of PRDX6 Correlates with Migration and Invasiveness of Colorectal Cancer Cells

Effects of autophagy regulation of tumor-associated macrophages on radiosensitivity of colorectal cancer cells

Functions of nuclear actin-binding proteins in human cancer (Review)

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