Insulin-like Growth Factor I Controls Adhesion Strength Mediated by α(5)β(1) Integrins in Motile Carcinoma Cells

One of the intriguing questions regarding cell motility concerns the mechanism that makes stationary cells move. Here, we provide the first physical evidence that the onset of breast cancer cell motility in response to insulin-like growth factor I (IGF-I) correlates with lowering of adhesion strength from 2.52 ± 0.20 to 1.52 ± 0.13 μdynes/μm(2) in cells attached to fibronectin via α(5)β(1) integrin. The adhesion strength depends on the dose of IGF-I and time of IGF-I treatment. Weakening of cell-matrix adhesion is blocked significantly (p < 0.01) by the catalytically inactive IGF-I receptor (IGF-IR) and the phosphoinositide 3-kinase (PI-3 kinase) inhibitor LY-294002, but it is unaffected by mitogen-activated protein kinase kinase inhibitor UO-126 and Src kinase inhibitor PP2. Sustained blockade of Rho-associated kinase (ROCK) with Y-27632 down-regulates adhesion strength in stationary, but not in IGF-I-treated, cells. Jasplakinolide, a drug that prevents actin filament disassembly, counteracts the effect of IGF-I on integrin-mediated cell adhesion. In the absence of growth factor signaling, ROCK supports a strong adhesion via α(5)β(1) integrin, whereas activation of the IGF-IR kinase reduces cell-matrix adhesion through a PI-3K-dependent, but ROCK-independent, mechanism. We propose that disassembly of the actin filaments via PI-3 kinase pathway contributes to weakening of adhesion strength and induction of cell movement. Understanding how cell adhesion and migration are coordinated has an important application in cancer research, developmental biology, and tissue bioengineering

Rap2A Is Upregulated in Invasive Cells Dissected from Follicular Thyroid Cancer

The development of molecular biomarkers (BMs) of follicular thyroid carcinoma is aimed at advancing diagnosis of follicular neoplasm, as histological examination of those tumors does not lend itself to definitive diagnosis of carcinoma. We assessed the relative levels of expression of 6 genes: CCND2, PCSK2, PLAB, RAP2A, TSHR, and IGF-1R in archived thyroid tissue. The quantitative real-time PCR analysis revealed a significant change in 3 genes: PSCK2 (a 22.4-fold decrease, =2.81−2), PLAB (an 8.3-fold increase, =9.81−12), and RAP2A (a 6.3-fold increase, =9.13−10) in carcinoma compared with adenoma. Expression of PCSK2 was equally low, PLAB was equally high, whereas RAP2A expression was significantly higher (25.9-fold, =0.039) in microdissected carcinoma cells that have invaded through the thyroid capsule and entered blood vessels than in thyroid tumor cells growing under the capsule. Thus, RAP2A appeared as a unique and worthy of further evaluation candidate BM associated with invasion of thyroid follicular cells