Apoptotic effect of imatinib on human colon adenocarcinoma cells: Influence on actin cytoskeleton organization and cell migration

Popow-Woźniak, Agnieszka; Woźniakowska, Aleksandra; Kaczmarek, Ł.; Malicka-Błaszkiewicz, Maria; Nowak, Dorota

doi:10.1016/j.ejphar.2011.05.036

Cited by 12 publications

(16 citation statements)

References 43 publications

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“…These findings are in line with our studies showing that c-Kit promotes colorectal cancer cell proliferation both in vitro and in vivo. An additional study (39) with this inhibitor showed a reduction in the proliferation and transwell migration of LS180 cells in contrast to our findings on the effect of c-Kit on cell motility. Because EGF was used to stimulate the migration of LS180 cells, this could conceivably activate signaling pathways that are inhibited by imatinib (such as the Brc/Abl pathway), independently of c-Kit activity.…”

Section: Discussioncontrasting

confidence: 55%

c-Kit Is Suppressed in Human Colon Cancer Tissue and Contributes to L1-Mediated Metastasis

Gavert

Shvab

Sheffer³

et al. 2013

Cancer Research

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The transmembrane neural cell adhesion receptor L1 is a Wnt/b-catenin target gene expressed in many tumor types. In human colorectal cancer, L1 localizes preferentially to the invasive front of tumors and when overexpressed in colorectal cancer cells, it facilitates their metastasis to the liver. In this study, we investigated genes that are regulated in human colorectal cancer and by the L1-NF-kB pathway that has been implicated in liver metastasis. c-Kit was the most highly suppressed gene in both colorectal cancer tissue and the L1-NF-kB pathway. c-Kit suppression that resulted from L1-mediated signaling relied upon NF-kB, which directly inhibited the transcription of SP1, a major activator of the c-Kit gene promoter. Reconstituting c-Kit expression in L1-transfected cells blocked the biological effects conferred by L1 overexpression in driving motility and liver metastasis. We found that c-Kit expression in colorectal cancer cells is associated with a more pronounced epithelial morphology, along with increased expression of E-cadherin and decreased expression of Slug. Although c-Kit overexpression inhibited the motility and metastasis of L1-expressing colorectal cancer cells, it enhanced colorectal cancer cell proliferation and tumorigenesis, arguing that separate pathways mediate tumorigenicity and metastasis by c-Kit. Our findings provide insights into how colorectal cancer metastasizes to the liver, the most common site of dissemination in this cancer. Cancer Res; 73(18); 5754-63. Ó2013 AACR.

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Section: Discussioncontrasting

confidence: 55%

c-Kit Is Suppressed in Human Colon Cancer Tissue and Contributes to L1-Mediated Metastasis

Gavert

Shvab

Sheffer³

et al. 2013

Cancer Research

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“…Tyrosine kinase and PKC are both related with actin cytoskeleton. On the one hand, STI571 apoptotic effect is associated with actin cytoskeleton alteration in HMC-1 560 cell line, accompanied by actin filamentous aggregation and actin polymerization decrease [37]. On the other hand, it was described that PKC isoforms binding to F-actin enhances isozymes activity [38].…”

Section: Resultsmentioning

confidence: 98%

Cross-talks between c-Kit and PKC isoforms in HMC-1560 and HMC-1560,816 cells. Different role of PKCδ in each cellular line

Tobío

Alfonso

Botana

2015

Cellular Immunology

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The c-kit inhibitor STI571 represents one of the most important treatments for patients with mastocytosis. However, intracellular pathways modulated by this compound are not completely defined. Here, STI571 effect on Protein Kinase C (PKC) regulation is determined in HMC-1 mast cell lines. STI571 activates PKCδ isoform resulting in HMC-1(560) apoptosis. The apoptosis observed is PKCδ-dependent, since PKCδ-silencing avoids STI571 effect. c-kit inhibition implies nuclear PKCδ translocation characterized by a clear dependence on actin cytoskeleton integrity in HMC-1(560) cell line, but not in HMC-1(560,816). Therefore, PKCδ modulations can lead to a serious decrease in STI571 treatment-effectiveness.

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“…In former studies imatinib also showed inhibitory impact on the PTK receptor c-kit and on its PTK activity (33,35). Thus, imatinib has antitumor activities towards adenocarcinoma, e.g., colon cancer, and its antitumoral effects have also been shown in non-small cell lung cancer and HNSCC (36,37). In concequence, we set up the above study to analyze its potency in HNSCC cell lines to confirm these effects.…”

Section: Discussionmentioning

confidence: 99%

Alteration of MMP-2 and -14 expression by imatinib in HPV-positive and -negative squamous cell carcinoma

et al. 2012

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Abstract. Head and neck squamous cell carcinoma (HNSCC)is an aggressive epithelial malignancy. It is known to be the most common neoplasm appearing in the upper aerodigestive tract. The poor 5-year survival rate has remained unchanged in the last decades even though improved techniques in surgery, radiation and chemotherapy have been established. In contrast to the overall decreasing incidence of head and neck cancer in the US, the incidence of HPV-associated oropharyngeal cancer is increasing, indicating the importance of viral etiology. Furthermore, growth and invasion of HNSCC are strongly influenced by the extracellular matrix (ECM). Matrix metalloproteinases (MMP) have been shown to play key roles in the remodeling of the ECM. Imatinib (STI 571) was originally designed to inhibit the BCR-ABL tyrosine kinase in chronic myeloid leukaemia. But it also has an inhibitory impact, e.g., on the protein-tyrosine-kinase (PTK) receptor c-kit and on its PTK activity in HNSCC. In this study, we incubated the HNSCC cell lines HNSCC 11A and 14C and the p16-positive SCC line CERV196 with increasing concentrations of imatinib or carboplatin. After an incubation time of up to 10 days, we evaluated MMP-2 and -14 expression by ELISA techniques and immunohistochemistry. MMP-2 and -14 expression was demonstrated in all incubated tumor cell lines. Especially incubation with imatinib resulted in a significant decrease in MMP expression in incubated cell lines. Our results indicate that the expression of MMP-2 and -14 is suppressed in the presence of imatinib. Thus, imatinib may exert in part its inhibitory effect on malignant cell growth via the blockage of the signal transduction of PTK receptors. Further studies are warranted, especially keeping in mind the moderate toxicity of imatinib.

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Apoptotic effect of imatinib on human colon adenocarcinoma cells: Influence on actin cytoskeleton organization and cell migration

Cited by 12 publications

References 43 publications

c-Kit Is Suppressed in Human Colon Cancer Tissue and Contributes to L1-Mediated Metastasis

c-Kit Is Suppressed in Human Colon Cancer Tissue and Contributes to L1-Mediated Metastasis

Cross-talks between c-Kit and PKC isoforms in HMC-1560 and HMC-1560,816 cells. Different role of PKCδ in each cellular line

Alteration of MMP-2 and -14 expression by imatinib in HPV-positive and -negative squamous cell carcinoma

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