The role of human pituitary transforming gene-1 in transcriptional and cytoskeletal regulation of cancer cells

Yi-Chu Liao^a, Ji-Hsiung Chen^b

^a Department of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan
^b Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan

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Abstract
Human pituitary tumor-transforming gene-1 (hPTTG1) is an oncogene that is expressed at a high level in most tumors, especially in metastatic ones. Accumulating evidence reveals that hPTTG1 is a trancription factor that has transcriptional activity either by directly or indirectly binding to DNA. Furthermore, hPTTG1 has been identified to regulate Rho guanine nucleotide exchange factor-H1 (GEF-H1) directly, by an interaction with microtubules and contributes to cancer progression. GEF-H1 activity is important for RhoA-dependent changes in cell morphology and actin organization. hPTTG1 activates GEF-H1/RhoA signaling to affect cytoskeleton organization, cell motility, cell invasion, and breast cancer metastasis. Thus, hPTTG1 links changes in microtubule integrity to RhoA-dependent regulation of the actin cytoskeleton, and therefore promotes cancer metastasis. The molecular mechanism that links microtubule dynamics to RhoA-GTPases has not, as yet, been elucidated.

Keywords
Breast cancer metastasis; Cytoskeleton regulation; GEF-H1; hPTTG1; RhoA