Abstract
The T-box transcription factors Tbx2 and Tbx3 are overexpressed in many cancers and in melanoma promote proliferation by actively suppressing senescence. Whether they also contribute to tumor progression via other mechanisms is not known. Here, we identify a novel role for these factors, providing evidence that Tbx3, and potentially Tbx2, directly repress the expression of E-cadherin, a keratinocyte-melanoma adhesion molecule whose loss is required for the acquisition of an invasive phenotype. Overexpression of Tbx2 and Tbx3 in melanoma cells down-regulates endogenous E-cadherin expression, whereas depletion of Tbx3, but not Tbx2, increases E-cadherin mRNA and protein levels and decreases melanoma invasiveness in vitro. Consistent with these observations, in melanoma tissue, Tbx3 and E-cadherin expression are inversely correlated. Depletion of Tbx3 also leads to substantial up-regulation of Tbx2. The results suggest that Tbx2 and Tbx3 may play a dual role during the radial to vertical growth phase transition by both inhibiting senescence via repression of p21CIP1 expression, and enhancing melanoma invasiveness by decreasing E-cadherin levels.
| Original language | English |
|---|---|
| Pages (from-to) | 7872-7881 |
| Number of pages | 10 |
| Journal | Cancer Research |
| Volume | 68 |
| Issue number | 19 |
| DOIs | |
| Publication status | Published - Oct 1 2008 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
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Tbx3 represses E-cadherin expression and enhances melanoma invasiveness. / Rodriguez, Mercedes; Aladowicz, Ewa; Lanfrancone, Luisa; Goding, Colin R.
In: Cancer Research, Vol. 68, No. 19, 01.10.2008, p. 7872-7881.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Tbx3 represses E-cadherin expression and enhances melanoma invasiveness
AU - Rodriguez, Mercedes
AU - Aladowicz, Ewa
AU - Lanfrancone, Luisa
AU - Goding, Colin R.
PY - 2008/10/1
Y1 - 2008/10/1
N2 - The T-box transcription factors Tbx2 and Tbx3 are overexpressed in many cancers and in melanoma promote proliferation by actively suppressing senescence. Whether they also contribute to tumor progression via other mechanisms is not known. Here, we identify a novel role for these factors, providing evidence that Tbx3, and potentially Tbx2, directly repress the expression of E-cadherin, a keratinocyte-melanoma adhesion molecule whose loss is required for the acquisition of an invasive phenotype. Overexpression of Tbx2 and Tbx3 in melanoma cells down-regulates endogenous E-cadherin expression, whereas depletion of Tbx3, but not Tbx2, increases E-cadherin mRNA and protein levels and decreases melanoma invasiveness in vitro. Consistent with these observations, in melanoma tissue, Tbx3 and E-cadherin expression are inversely correlated. Depletion of Tbx3 also leads to substantial up-regulation of Tbx2. The results suggest that Tbx2 and Tbx3 may play a dual role during the radial to vertical growth phase transition by both inhibiting senescence via repression of p21CIP1 expression, and enhancing melanoma invasiveness by decreasing E-cadherin levels.
AB - The T-box transcription factors Tbx2 and Tbx3 are overexpressed in many cancers and in melanoma promote proliferation by actively suppressing senescence. Whether they also contribute to tumor progression via other mechanisms is not known. Here, we identify a novel role for these factors, providing evidence that Tbx3, and potentially Tbx2, directly repress the expression of E-cadherin, a keratinocyte-melanoma adhesion molecule whose loss is required for the acquisition of an invasive phenotype. Overexpression of Tbx2 and Tbx3 in melanoma cells down-regulates endogenous E-cadherin expression, whereas depletion of Tbx3, but not Tbx2, increases E-cadherin mRNA and protein levels and decreases melanoma invasiveness in vitro. Consistent with these observations, in melanoma tissue, Tbx3 and E-cadherin expression are inversely correlated. Depletion of Tbx3 also leads to substantial up-regulation of Tbx2. The results suggest that Tbx2 and Tbx3 may play a dual role during the radial to vertical growth phase transition by both inhibiting senescence via repression of p21CIP1 expression, and enhancing melanoma invasiveness by decreasing E-cadherin levels.
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UR - http://www.scopus.com/inward/citedby.url?scp=54249133490&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-08-0301
DO - 10.1158/0008-5472.CAN-08-0301
M3 - Article
C2 - 18829543
AN - SCOPUS:54249133490
VL - 68
SP - 7872
EP - 7881
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 19
ER -