Journal of Biosciences

, Volume 42, Issue 3, pp 491–499 | Cite as

Hypoxia stimulates invasion and migration of human cervical cancer cell lines HeLa/SiHa through the Rab11 trafficking of integrin αvβ3/FAK/PI3K pathway-mediated Rac1 activation

  • Hao Xu
  • Yuan Yuan
  • Wenqian Wu
  • Min Zhou
  • Qian Jiang
  • Linjun Niu
  • Jiayin Ji
  • Nianli Liu
  • Longzhen Zhang
  • Xia WangEmail author


Hypoxia plays a key role in tumour cell survival, invasion, and metastasis. An increasing number of studies have attempted to characterize the tumour response to hypoxia and to identify predictive markers of disease. Here we show that hypoxia increases tumour cell invasion and migration by the modulation of Rab11, an important molecule for vesicular trafficking. In our study, we found that Rab11, together with the activation of Rac1, could stimulate invasion and migration of cervical cancer cell lines HeLa/SiHa in hypoxia. Activation of Rac1 activity by hypoxia seems to be central to carcinoma invasion. We also found that these effects could be related to the integrin αvβ3. In addition, we studied the molecular pathway for this process. Our results showed that in cervical cancer cell lines HeLa/SiHa, Rac1 activation in hypoxia could stimulate invasion and migration, and this process was mediated by integrin αvβ3-mediated FAK and PI3K phosphorylation. Furthermore, hypoxia induced a dramatic increase in αvβ3 integrin surface expression, and this increase is dependent on Rab11. In conclusion, our study might provide a new mechanism for the effect of hypoxia on stimulating cervical carcinoma invasion.


Cervical cancer hypoxia Rab11 Rac1 αvβ3/FAK/PI3K 



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Copyright information

© Indian Academy of Sciences 2017

Authors and Affiliations

  • Hao Xu
    • 1
  • Yuan Yuan
    • 2
  • Wenqian Wu
    • 3
  • Min Zhou
    • 4
  • Qian Jiang
    • 1
  • Linjun Niu
    • 5
  • Jiayin Ji
    • 1
  • Nianli Liu
    • 6
  • Longzhen Zhang
    • 1
  • Xia Wang
    • 1
    Email author
  1. 1.Department of RadiotherapyThe Affiliated Hospital of Xuzhou Medical UniversityXuzhouChina
  2. 2.Department of OncologyThe Affiliated Hospital of Xuzhou Medical UniversityXuzhouChina
  3. 3.Department of ImmunologyThe Affiliated Hospital of Xuzhou Medical UniversityXuzhouChina
  4. 4.Intensive Care UnitThe Affiliated Hospital of Xuzhou Medical UniversityXuzhouChina
  5. 5.Department of Interventional RadiologyThe Affiliated Hospital of Xuzhou Medical UniversityXuzhouChina
  6. 6.Tumor Biological Therapy InstituteXuzhou Medical UniversityXuzhouChina

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