Kornberg Lori, Fleigel Jeffery
Department of Otolaryngology, Box 100264, 1600 SW Archer Road, Room M-228, University of Florida, Gainesville, FL 32610, USA.
Anticancer Res. 2003 Jan-Feb;23(1A):91-7.
Focal adhesion kinase (FAK), which has received much attention as a transducer of integrin-mediated signals, is overexpressed in several types of human cancer. FAK-related non-kinase (FRNK) is an autonomously expressed carboxyl-terminal region of FAK, which acts as an inhibitor of FAK function. In order to determine the role of FAK/FRNK in cancer, we constructed a transformed human embryonic kidney cell line (293), which overexpressess FRNK in an inducible manner. Cells that overexpress FRNK have reduced adhesion-mediated tyrosine phosphorylation of FAK with a coincident decrease in ERK phosphorylation. FRNK overexpression did not restore anoikis to these transformed cells. However, FRNK overexpression did sensitize cells to the cytotoxic effect of 5-fluorouracil and led to a decrease in haptotactic mobility. We conclude that in these transformed cells the predominant effect of FAK is on cell migration. Additionally, overexpression of FRNK may provide therapeutic benefits by enhancing the cytotoxic effects of chemotherapeutic agents.
粘着斑激酶（FAK）作为整合素介导信号的转导分子备受关注，在多种人类癌症中过度表达。FAK相关非激酶（FRNK）是FAK自主表达的羧基末端区域，作为FAK功能的抑制剂发挥作用。为了确定FAK/FRNK在癌症中的作用，我们构建了一种转化的人胚肾细胞系（293），它以可诱导的方式过度表达FRNK。过度表达FRNK的细胞，其FAK的粘着介导酪氨酸磷酸化减少，同时ERK磷酸化也随之降低。FRNK的过度表达并未使这些转化细胞恢复失巢凋亡。然而，FRNK的过度表达确实使细胞对5-氟尿嘧啶的细胞毒性作用敏感，并导致趋触性迁移减少。我们得出结论，在这些转化细胞中，FAK的主要作用是影响细胞迁移。此外，FRNK的过度表达可能通过增强化疗药物的细胞毒性作用而提供治疗益处。
