Lewandowska U, Zelazowski M, Seta K, Byczewska M, Pluciennik E, Bednarek A K
Department of Medical Enzymology, Medical University of Lodz, Poland.
J Physiol Pharmacol. 2009 May;60 Suppl 1:47-56.
WWOX is a tumour suppressor gene affected in multiple cancers, especially in breast, prostate and ovary. This gene is located at the chromosomal area 16q23.3-24.1, which was identified as a common chromosomal fragile site FRA16D. WWOX turned out to possess tumour suppressor features despite the fact that the most basic (classical) way of tumour suppressor gene inactivation involves both alleles (e.g. through deletions, point mutations and promoter methylation), which is very rare event in a case of WWOX, occurring only in few cell lines. A large number of papers corroborate the phenomenon of correlation between the loss of WWOX expression and more aggressive/worse prognosis in many different types of tumours, for example breast cancer, nonsmall cell lung cancer, bladder cancer, gastric cancer or sporadic meningiomas. Ectopically increased WWOX expression promotes migration through basal membrane, however suppresses anchorage independent growth and induces normal-like colony formation in matrigel.
WWOX是一种在多种癌症中受影响的肿瘤抑制基因,尤其是在乳腺癌、前列腺癌和卵巢癌中。该基因位于染色体区域16q23.3 - 24.1,该区域被鉴定为常见的染色体脆弱位点FRA16D。尽管肿瘤抑制基因失活的最基本(经典)方式涉及两个等位基因(例如通过缺失、点突变和启动子甲基化),但WWOX却表现出肿瘤抑制特性,而这种情况在WWOX中非常罕见,仅在少数细胞系中发生。大量论文证实了在许多不同类型的肿瘤中,如乳腺癌、非小细胞肺癌、膀胱癌、胃癌或散发性脑膜瘤,WWOX表达缺失与更具侵袭性/更差预后之间的相关性现象。异位增加的WWOX表达促进穿过基底膜的迁移,但抑制非锚定依赖性生长并在基质胶中诱导形成正常样集落。