Tumor Biology

, Volume 37, Issue 2, pp 2555–2563 | Cite as

EGF enhances low-invasive cancer cell invasion by promoting IMP-3 expression

Original Article


The initiation and progression of cancer is closely associated with the tumor microenvironment. The overexpression of oncogenes during tumor growth and progression by stromal stimuli can affect the aggressiveness of the cancer. In this study, in vitro and in vivo studies were performed to examine the role of stromal epidermal growth factor (EGF) in enhancing the invasive potential of in low-invasive cancer. EGF was tested in order to elucidate the specific molecules that participate in increasing the invasive potential of low-invasive cancer cells. EGF stimulation enhanced cancer invasion in an EGF receptor (EGFR)-dependent manner. EGF induced insulin-like growth factor-II mRNA-binding protein-3 (IMP-3) and podoplanin (PDPN) expression, which play an important role in oral squamous cell carcinoma (OSCC) cell invasion. An apparent tumor mass was not observed in the mouse xenograft; however, multiple tumor microfoci were seen in mice injected with IMP-3-overexpressing cells. These results show that EGF stimulates IMP-3 expression, thereby increasing cancer invasion and tumor progression.


Epidermal growth factor Stroma IMP-3 PDPN Invasion 



Epidermal growth factor


Insulin-like growth factor-II mRNA-binding protein-3




Epidermal growth factor receptor


Oral squamous cell carcinoma



This work was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (1120190), and by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012R1A1A2040564).

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Xianglan Zhang
    • 2
    • 3
  • Im-hee Jung
    • 1
  • Young Sun Hwang
    • 1
  1. 1.Department of Dental Hygiene, College of Health ScienceEulji UniversitySeongnamRepublic of Korea
  2. 2.Oral Cancer Research InstituteYonsei University College of DentistrySeoulRepublic of Korea
  3. 3.Department of PathologyYanbian University HospitalYanji CityChina

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