The HIF-1α/CXCR4 pathway supports hypoxia-induced metastasis of human osteosarcoma cells

Guan, Guofeng; Zhang, Yinglong; Lu, Yao; Liu, Lijuan; Shi, Doufei; Yuan, Wen; Yang, Lijun; Ma, Qiang; Liu, Tao; Zhu, Xiaodong; Qiu, Xiuchun; Zhou, Yong

doi:10.1016/j.canlet.2014.11.034

Cited by 94 publications

(81 citation statements)

References 47 publications

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“…Cancer stem cells (CSCs) exhibit properties of embryonic stem cells such as self-renewal, pluripotency, and metastatic potential [88, 89]. Although they constitute a minor portion of the total cancer cell population [90, 91], CSCs can repopulate tumors following therapy leading to a more aggressive and resistant phenotype.…”

Section: Hif Upregulation In Cancer: Consequencesmentioning

confidence: 99%

Hypoxia-Inducible Factors and Cancer

Jun

Rathore

Younas

et al. 2017

Curr Sleep Medicine Rep

198

119

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Purpose Of Review Hypoxia inducible factors (HIFs) mediate the transcription of hundreds of genes that allow cells to adapt to hypoxic environments. In this review, we summarize the current state of knowledge about mechanisms of HIF activation in cancer, as well as downstream cancer-promoting consequences such as altered substrate metabolism, angiogenesis, and cell differentiation. In addition, we examine the proposed relationship between respiratory-related hypoxia, HIFs, and cancer. Recent Findings HIFs are increased in many forms of cancer, and portend a poor prognosis and response to therapy. Conclusion HIFs play a critical role in various stages of carcinogenesis. HIF and its transcription targets may be useful as biomarkers of disease and therapeutic targets for cancer.

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Section: Hif Upregulation In Cancer: Consequencesmentioning

confidence: 99%

Hypoxia-Inducible Factors and Cancer

Jun

Rathore

Younas

et al. 2017

Curr Sleep Medicine Rep

198

119

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“…Mounting evidences have reported the crucial function of chemokines and their receptors in cancer. For example, CXCR4 has been found to be involved with metastasis in more than 20 different cancers [5–7]. In CRC, the study by Kawada et al revealed that CXCR3 could promote cancer metastasis to lymph nodes [8].…”

Section: Introductionmentioning

confidence: 99%

CCR4 promotes metastasis via ERK/NF-κB/MMP13 pathway and acts downstream of TNF-α in colorectal cancer

Zhao

Guan

et al. 2016

Oncotarget

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Chemokines and chemokine receptors are causally involved in the metastasis of human malignancies. As a crucial chemokine receptor for mediating immune homeostasis, however, the role of CCR4 in colorectal cancer (CRC) remains unknown. In this study, we found that high expression of CCR4 in CRC tissues was correlated with shorter overall survival and disease free survival. In vitro and in vivo experiments revealed that silencing CCR4 attenuated the invasion and metastasis of CRC cells, whereas ectopic overexpression of CCR4 contributed to the forced metastasis of these cells. We further demonstrated that matrix metalloproteinase 13 (MMP13) played an important role in CCR4-mediated cancer cell invasion, which is up-regulated by ERK/NF-κB signaling. Positive correlation between CCR4 and MMP13 expression was also observed in CRC tissues. Moreover, our investigations showed that the level of CCR4 could be induced by TNF-α dependent of NF-κB activation in CRC cells. CCR4 might be implicated in TNF-α-regulated cancer cells metastasis. Combination of CCR4 and TNF-α is a more powerful prognostic marker for CRC patients. These findings suggest that CCR4 facilitates metastasis through ERK/NF-κB/MMP13 signaling and acts as a downstream target of TNF-α. CCR4 inhibition may be a promising therapeutic option for suppressing CRC metastasis.

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“…A large number of studies already confirmed that hypoxia could induce autophagy [135][136][137]. More intriguing is that hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a heterodimeric transcription factor that mediates adaptive responses to hypoxia and can also be induced under anoxic condition [138][139][140]. In view of the above fact that hypoxia can activate HIF-1 alpha, and can also promote autophagy, the problem whether HIF-1 alpha could regulate autophagy under anoxic condition has been lingering in the minds of scholars.…”

Section: The Focus Of Autophagy Regulation: Hif-1 Alphamentioning

confidence: 97%