Transformation of rat intestinal epithelial cells by overexpression of Rab25 is microtubule dependent.
Little research has addressed the role of membrane trafficking and recycling in the regulation of the transformed phenotype of neoplastic cells. The small GTPase Rab25 is an epithelial-specific modulator of membrane recycling. Recent studies have demonstrated that Rab25 expression is up-regulated in a number of epithelial cancers and overexpression may increase the aggressive phenotype of certain cancers. We have utilized the nontransformed RIE cell line to examine the influence of Rab25 on transformation. Overexpression of Rab25 in RIE cells leads to morphological transformation as well as growth in soft agar, tumor formation in nude mice, disruption of integrin-based focal adhesions, and alteration in modified microtubule subsets. Although the predominance of recent cancer research has focused on the manipulation of the actin-based cytoskeleton, recycling trafficking relies on microtubules. Transformation of RIE cells through overexpression of Rab25, but not with H-Ras(V12) , was reversed by inhibitors of microtubule polymerization. These results suggest that up-regulation of Rab25 in RIE cells leads to microtubule-dependent transformation. Thus, depolymerization of microtubules may be a potent therapeutic target for cancer therapy through the reversal of the invasive phenotype of certain cancer cells.
Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Lynne A
LA
Lapierre
Cathy M
CM
Caldwell
James N
JN
Higginbotham
Kenya M
KM
Avant
Janine
J
Hall
R Daniel
RD
Beauchamp
James R
JR
Goldenring
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015689:Oncogene Protein p21(ras) / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014183:Transplantation, Heterologous; D020691:rab GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics
D015689:Oncogene Protein p21(ras); D020691:rab GTP-Binding Proteins
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