Loss of the integrin-activating transmembrane protein Fam38A (Piezo1) promotes a switch to a reduced integrin-dependent mode of cell migration.
Loss of the integrin-activating transmembrane protein Fam38A (Piezo1) promotes a switch to a reduced integrin-dependent mode of cell migration.
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DOI：
10.1371/journal.pone.0040346
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Sethi T
中科院分区：
文献类型：
--
作者：
McHugh BJ;Murdoch A;Haslett C;Sethi T
肺癌是发达国家最常见的致命疾病之一。这种疾病很少通过目前可用的治疗方法治愈，总体存活率为∼10%。因此，鉴定新的蛋白质，为肺癌的侵袭和转移过程提供关键的见解，可能会提供急需的预后标记物，并影响治疗策略。整合素异二聚体细胞表面受体家族的功能异常是癌症的一个共同主题--研究新的整合素活性调节因子可能为肿瘤的侵袭和转移过程提供重要的见解，并可能揭示潜在的治疗靶点。我们先前曾报道，位于内质网(ER)的新型多跨膜结构域蛋白Fam38A的缺失会使内源性β1整合素亲和力失活，从而减少细胞黏附。我们现在发现，Fam38A的缺失，也被称为Piezo1，导致锚定独立，并切换到减少整合素依赖的细胞迁移/侵袭模式，这是这种整合素调节蛋白的一种新表型。正常肺上皮细胞在2D时间推移显微镜下显示出更高的迁移速度和侵袭到基质细胞的能力，尽管整合素亲和力降低。我们证实，在小细胞肺癌(SCLC)系中，FAM38A的表达大大减少，其中一种形式的整合素依赖减少的迁移，即阿米巴迁移，是一种已知的表型。我们认为，Fam38A表达的缺失可能导致肺癌细胞迁移和转移的增加。
Lung cancer is one of the most common fatal diseases in the developed world. The disease is rarely cured by currently available therapies, with an overall survival rate of ∼10%. Characterizing novel proteins that offer crucial insights into the processes of lung tumour invasion and metastasis may therefore provide much-needed prognostic markers, and influence therapeutic strategies. Aberrant function of the integrin family of heterodimeric cell surface receptors is a common theme in cancer - investigation into novel integrin activity regulators may offer crucial insights into the processes of tumour invasion and metastasis and may reveal insights into potential therapeutic targets. We previously described that depletion of the novel multi-transmembrane domain protein Fam38A, located at the endoplasmic reticulum (ER), inactivates endogenous beta1 integrin affinity, reducing cell adhesion. We now show that depletion of Fam38A, also now known as Piezo1, causes anchorage independence and a switch to a reduced integrin-dependent mode of cell migration/invasion, a novel phenotype for this integrin-regulating protein. Normal lung epithelial cells show increased rates of migration by 2D time-lapse microscopy and increased capacity to invade into matrigel, despite having decreased integrin affinity. We confirm greatly depleted Fam38A expression in small cell lung cancer (SCLC) lines where a form of reduced integrin-dependent migration, i.e. amoeboid migration, is a known phenotype. We propose that loss of Fam38A expression may cause increased cell migration and metastasis in lung tumours.
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DOI：
10.1083/jcb.139.3.575
发表时间：
1997-11-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Schwartz MA
通讯作者：
Schwartz MA
影响因子：
2.2
作者：
Takeuchi, Tomoyo;Minami, Yuko;Noguchi, Masayuki
通讯作者：
Noguchi, Masayuki
影响因子：
21.3
作者：
Katz, Menachem;Amit, Ido;Yarden, Yosef
通讯作者：
Yarden, Yosef
影响因子：
4.8
作者：
Hodkinson, Philip S.;Elliott, Paul. A.;Sethi, Tariq
通讯作者：
Sethi, Tariq
DOI：
10.1083/jcb.200405155
发表时间：
2004-11-22
期刊：
The Journal of cell biology
影响因子：
--
作者：
McHugh B;Krause SA;Yu B;Deans AM;Heasman S;McLaughlin P;Heck MM
通讯作者：
Heck MM