Stem Cell Factor/c-kit Receptor Signaling Enhances the Proliferation and Invasion of Colorectal Cancer Cells Through the PI3K/Akt Pathway

Yasuda, Akira; Sawai, Hirozumi; Takahashi, Hiroki; Ochi, Nobuo; Matsuo, Yoichi; Funahashi, Hitoshi; Sato, Mikinori; Okada, Yuji; Takeyama, Hiromitsu; Manabe, Tadao

doi:10.1007/s10620-007-9759-7

Cited by 89 publications

(84 citation statements)

References 30 publications

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“…They also have been implicated in inflammatory diseases, tissue remodeling-including fibrosis-and in liver regeneration after liver injury (Simpson et al 2003;Krieg et al 2006;Reber et al 2006). However, further studies indicate that, in addition to its physiological functions, in combination with stem cell factor, c-kit plays an important role in carcinogenesis in various tumors (Sun et al 2006;Yasuda et al 2007). Following to Mansuroglu et al (2009), liver cells will upregulate the stem cell factor or/and CD117 during cholangiocarcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Doxorubicin and 5-fluorouracil resistant hepatic cancer cells demonstrate stem-like properties

Nguyen

Tran³

et al. 2012

Cytotechnology

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The efficacy of hepatocellular carcinoma (HCC) treatment is very low because of the high percentage of recurrence and resistance to anticancer agents. Hepatic cancer stem cells (HCSCs) are considered the origin of such recurrence and resistance. Our aim was to evaluate the stemness of doxorubicin and 5-fluorouracil resistant hepatic cancer cells and establish the new method to isolate the HCSCs from primary cultured HCC tumors. HCC biopsies were used to establish primary cultures. Then, primary cells were selected for HCSCs by culture in medium supplemented with doxorubicin (0, 0.1, 0.25, 0.5 or 1 lg/mL), 5-fluorouracil (0, 0.1, 0.25, 0.5 or 1 lg/mL) or their combination. Selection was confirmed by detection of HCSC markers such as CD133, CD13, CD90, and the side population was identified by rhodamine 123 efflux. The cell population with the strongest expression of these markers was used to evaluate the cell cycle, gene expression profile, tumor sphere formation, marker protein expression, and in vivo tumorigenesis. Selective culture of primary cells in medium supplemented with 0.5 lg/mL doxorubicin and 1 lg/mL 5-fluorouracil selected cancer cells with the highest stemness properties. Selected cells strongly expressed CD13, CD133, CD90, and CD326, efflux rhodamine 123 and formed tumor spheres in suspension. Moreover, selected cells were induced to differentiate into cells with high expression of CD19 and AFP (alpha-fetoprotein), and importantly, could form tumors in NOD/SCID mice upon injection of 1 9 10 5 cells/mouse. Selective culture with doxorubicin and 5-fluorouracil will enrich HCSCs, is an easy method to obtain HCSCs that can be used to develop better therapeutic strategies for patients with HCC, and particularly HCSC-targeting therapy.

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Section: Discussionmentioning

confidence: 99%

Doxorubicin and 5-fluorouracil resistant hepatic cancer cells demonstrate stem-like properties

Nguyen

Tran³

et al. 2012

Cytotechnology

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“…The developing human pancreas and multiple human pancreatic cancer cell lines express both c-Kit and SCF (Table 1) [11,49,53,56]. c-Kit + cells were detected at the earliest stage of human pancreatic development, as single endocrine cells differentiated from ducts [49].…”

Section: C-kit In the Developing Human Pancreasmentioning

confidence: 99%

A survival Kit for pancreatic beta cells: stem cell factor and c-Kit receptor tyrosine kinase

et al. 2015

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The interactions between c-Kit and its ligand, stem cell factor (SCF), play an important role in haematopoiesis, pigmentation and gametogenesis. c-Kit is also found in the pancreas, and recent studies have revealed that c-Kit marks a subpopulation of highly proliferative pancreatic endocrine cells that may harbour islet precursors. c-Kit governs and maintains pancreatic endocrine cell maturation and function via multiple signalling pathways. In this review we address the importance of c-Kit signalling within the pancreas, including its profound role in islet morphogenesis, islet vascularisation, and beta cell survival and function. We also discuss the impact of c-Kit signalling in pancreatic disease and the use of c-Kit as a potential target for the development of cell-based and novel drug therapies in the treatment of diabetes.

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“…20 GSK3b activity is regulated through the canonical Wnt signaling pathway, 21 also it is modulated by the phosphatidylinositol 3 kinase/Akt (PI3K/Akt). 22 It has been shown that PI3K activity is regulated by stem cell factor (SCF)/c-Kit and platelet-derived growth factor receptor (PDGFR), 23,24 which are regulated by Notch4/Int3, 13 linking Notch4/Int3 to GSK3b. In eukaryotic cells, protein degradation occurs in the lysosomes, but the main mechanism of protein degradation is the ubiquitin-proteasome system.…”

Section: 2mentioning

confidence: 99%

Original Research: Featured Article: Imatinib mesylate (Gleevec) inhibits Notch and c-Myc signaling: Five-day treatment permanently rescues mammary development

Callahan

Chestnut

Raafat

2016

Exp Biol Med (Maywood)

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Wap-Int3 transgenic females expressing the Notch4 intracellular domain (designated Int3) from the whey acidic protein promoter exhibit two phenotypes in the mammary gland: blockage of lobuloalveolar development and lactation, and tumor development with 100% penetrance. Previously, we have shown that treatment of Wap-Int3 tumor bearing mice with Imatinib mesylate (Gleevec) is associated with complete regression of the tumor. In the present study, we show that treatment of Wap-Int3 mice during day 1 through day 6 of pregnancy with Gleevec leads to the restoration of their lobuloalveolar development and ability to lactate in subsequent pregnancies in absence of Gleevec treatment. In addition, these mice do not develop mammary tumors. We investigated the mechanism for Gleevec regulation of Notch signaling and found that Gleevec treatment results in a loss of Int3 protein but not of Int3 mRNA in HC11 mouse mammary epithelial cells expressing Int3. The addition of MG-132, a proteasome inhibitor, shows increased ubiquitination of Int3 in the presence of Gleevec. Thus, Gleevec affects the stability of Int3 by promoting the degradation of Int3 via E3 ubiquitin ligases targeting it for the proteasome degradation. Gleevec is a tyrosine kinase inhibitor that acts on c-Kit and PDGFR. Therefore, we investigated the downstream substrate kinase GSK3b to ascertain the possible role that this kinase might play in the stability of Int3. Data show that Gleevec degradation of Int3 is GSK3b dependent. We have expanded our study of the effects Gleevec has on tumorigenesis of other oncogenes. We have found that anchorage-independent growth of HC11-c-Myc cells as well as tumor growth in nude mice is inhibited by Gleevec treatment. As with Int3, Gleevec treatment appears to destabilize the c-Myc protein but not mRNA. These results indicate that Gleevec could be a potential therapeutic drug for patients bearing Notch4 and/or c-Myc positive breast carcinomas.

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Stem Cell Factor/c-kit Receptor Signaling Enhances the Proliferation and Invasion of Colorectal Cancer Cells Through the PI3K/Akt Pathway

Cited by 89 publications

References 30 publications

Doxorubicin and 5-fluorouracil resistant hepatic cancer cells demonstrate stem-like properties

Doxorubicin and 5-fluorouracil resistant hepatic cancer cells demonstrate stem-like properties

A survival Kit for pancreatic beta cells: stem cell factor and c-Kit receptor tyrosine kinase

Original Research: Featured Article: Imatinib mesylate (Gleevec) inhibits Notch and c-Myc signaling: Five-day treatment permanently rescues mammary development

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