Expression of CD133 confers malignant potential by regulating metalloproteinases in human hepatocellular carcinoma

Kohga, Keisuke; Tatsumi, Tomohide; Takehara, Tetsuo; Tsunematsu, Hinako; Shimizu, Satoshi; Yamamoto, Masashi; Sasakawa, Akira; Miyagi, Takuya; Hayashi, Norio

doi:10.1016/j.jhep.2009.12.030

Cited by 86 publications

(71 citation statements)

References 25 publications

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“…Many specific cell surface markers have been identified and characterized at the biological and clinical level (8). Among these markers, CD133 and CD44 play a well-established role in the metastatic potential of LCSCs (8,10,14,42). notably, several recent studies reported that the expression of CD133 or CD44 alone is not sufficient to account for all of the biological properties of CSCs (43,44).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the number of spheres was significantly higher in the CD133 + /CD44 + subgroup (15 spheres/well) compared with the CD133 -/CD44 -subgroup (9 spheres/well) (Fig. 1C) contribute to CSC-associated cancer metastasis and invasion (10,14,39). Therefore, we performed in vitro Transwell migration and invasion assays to evaluate the metastatic potential of the Huh7 cell subpopulations.…”

Section: Cd133 + /Cd44mentioning

confidence: 98%

“…In addition, CD133 has been shown to mediate HCC metastasis by regulating the expression of metastasis-associated genes, and CD133 expression in HCC is associated with a poor prognosis (10)(11)(12). In our previous study, we demonstrated that Huh7 CD133 + liver cancer stem cells (LCSCs) exhibit greater metastatic potential compared with Huh7…”

Section: Elk3 Promotes the Migration And Invasion Of Liver Cancer Stementioning

confidence: 99%

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ELK3 promotes the migration and invasion of liver cancer stem cells by targeting HIF-1α

et al. 2016

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Abstract. Hepatocellular carcinoma (HCC) is the fifth most common solid cancer and the third most common cause of cancer-related mortality. HCC develops via a multistep process associated with genetic aberrations that facilitate HCC invasion and migration and promote metastasis. A growing body of evidence indicates that cancer stem cells (CSCs) are responsible for tumorigenesis, cancer cell invasion and metastasis. Despite the extremely small proportion of cancer cells represented by this subpopulation of HCC cells, CSCs play a key role in cancer metastasis and poor prognosis. ELK3 (Net/SAP-2/Erp) is a transcription factor that is activated by the Ras/extracellular signal-regulated kinase (ERK) signaling pathway. It plays several important roles in various physiological processes, including cell migration, invasion, wound healing, angiogenesis and tumorigenesis. In the present study, we investigated the role of ELK3 in cancer cell invasion and metastasis in CD133 + /CD44 + liver cancer stem cells (LCSCs). We isolated LCSCs expressing CD133 and CD44 from Huh7 HCC cells and evaluated their metastatic potential using invasion and migration assays. We found that CD133 + /CD44 + cells had increased metastatic potential compared with non-CD133 + /CD44 + cells. We also demonstrated that ELK3 expression was upregulated in CD133 + /CD44 + cells and that this aberration enhanced cell migration and invasion. In addition, we identified the molecular mechanism by which ELK3 promotes cancer cell migration and invasion. We found that silencing of ELK3 expression in CD133 + /CD44 + LCSCs attenuated their metastatic potential by modulating the expression of heat shock-induced factor-1α (HIF-1α). Collectively, the results of the present study demonstrated that ELK3 overexpression promoted metastasis in CD133 + /CD44 + cells by regulating HIF-1α expression and that silencing of ELK3 expression attenuated the metastatic potential of CD133 + /CD44 + LCSCs. In conclusion, modulation of ELK3 expression may represent a novel therapeutic strategy for preventing HCC metastasis and invasion.

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Section: Discussionmentioning

confidence: 99%

Section: Cd133 + /Cd44mentioning

confidence: 98%

Section: Elk3 Promotes the Migration And Invasion Of Liver Cancer Stementioning

confidence: 99%

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ELK3 promotes the migration and invasion of liver cancer stem cells by targeting HIF-1α

et al. 2016

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“…Furthermore, shared intracellular signaling pathways and cell surface proteins between cancer cells and stem cells have also supported the idea of the existence of stem-like cells with tumor-initiating capacity [3]. For example, the expression of the neural and hematopoietic stem cells marker CD133 has been found in numerous transformed tissues, such as the colon, brain, and liver [50–52]. These markers may also demonstrate functionality as knockdown of CD133 in hepatocellular carcinoma has been shown to decrease production of matrix metalloproteinases [50].…”

Section: Stem-like Basis For Human Malignanciesmentioning

confidence: 99%

“…For example, the expression of the neural and hematopoietic stem cells marker CD133 has been found in numerous transformed tissues, such as the colon, brain, and liver [50–52]. These markers may also demonstrate functionality as knockdown of CD133 in hepatocellular carcinoma has been shown to decrease production of matrix metalloproteinases [50]. As another example, dysregulation of the Hedgehog signaling pathway has been found in the cells of origin for basal cell carcinoma [53].…”

Section: Stem-like Basis For Human Malignanciesmentioning

confidence: 99%

Metastatic breast cancer cells in the bone marrow microenvironment: novel insights into oncoprotection

Patel

Dave²,

Murthy³

et al. 2010

Oncol Rev

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Among all cancers, malignancies of the breast are the second leading cause of cancer death in the United States after carcinoma of the lung. One of the major factors considered when assessing the prognosis of breast cancer patients is whether the tumor has metastasized to distant organs. Although the exact phenotype of the malignant cells responsible for metastasis and dormancy is still unknown, growing evidence has revealed that they may have stem cell-like properties that may account for resistance to chemotherapy and radiation. One process that has been attributed to primary tumor metastasis is the epithelial-to-mesenchymal transition. In this review, we specifically discuss breast cancer dissemination to the bone marrow and factors that ultimately serve to shelter and promote tumor growth, including the complex relationship between mesenchymal stem cells (MSCs) and various aspects of the immune system, carcinoma-associated fibroblasts, and the diverse components of the tumor microenvironment. A better understanding of the journey from the primary tumor site to the bone marrow and subsequently the oncoprotective role of MSCs and other factors within that microenvironment can potentially lead to development of novel therapeutic targets.

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Liver Cancer Stem Cells and Hepatocarcinogenesis

Okabe

Hayashi

Ishimoto

et al. 2015

Principles of Stem Cell Biology and Cancer

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Expression of CD133 confers malignant potential by regulating metalloproteinases in human hepatocellular carcinoma

Cited by 86 publications

References 25 publications

ELK3 promotes the migration and invasion of liver cancer stem cells by targeting HIF-1α

ELK3 promotes the migration and invasion of liver cancer stem cells by targeting HIF-1α

Metastatic breast cancer cells in the bone marrow microenvironment: novel insights into oncoprotection

Liver Cancer Stem Cells and Hepatocarcinogenesis

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