非小細(xì)胞肺癌（Non-small-cell carcinoma ）與“非小細(xì)胞癌”同義,。非小細(xì)胞型肺癌,，包括鱗癌,、腺癌,、大細(xì)胞癌,，與小細(xì)胞癌相比其癌細(xì)胞生長(zhǎng)分裂較慢，擴(kuò)散轉(zhuǎn)移相對(duì)較晚,。非小細(xì)胞肺癌約占肺癌總數(shù)的80-85%,。
肺腺癌一種人非小細(xì)胞肺癌（NSCLC）最常見(jiàn)的類型,，臨床以及基礎(chǔ)研究發(fā)現(xiàn)腫瘤組織中經(jīng)常高表達(dá)表皮生長(zhǎng)因子受體（EGFR）。然而,，EGFR的過(guò)度表達(dá)對(duì)肺腺癌的發(fā)病機(jī)制尚未完全了解,。
最近研究發(fā)現(xiàn)減少TIP30蛋白（30kDa艾滋病毒達(dá)相互作用蛋白-1）的表達(dá)與人非小細(xì)胞肺癌轉(zhuǎn)移相關(guān)，但TIP30蛋白的不足與非小細(xì)胞肺癌之間的因果關(guān)系尚不清楚,。近日,，Oncogene雜志上一則研究顯示，TIP30的缺失導(dǎo)致小鼠會(huì)自發(fā)形成肺腺瘤和腺癌,。異常擴(kuò)張的細(xì)支氣管肺泡干/祖細(xì)胞及肺泡Ⅱ型細(xì)胞會(huì)加速腫瘤發(fā)展,，也增加了TIP30敲除小鼠肺腫瘤組織中表皮生長(zhǎng)因子受體和其下游信號(hào)分子的表達(dá)。
此外,，人肺腺癌細(xì)胞敲除TIP30蛋白后,，造成EGFR活性EGFR上升，導(dǎo)致AKT的磷酸化ERK1 /2的表達(dá)上調(diào),。重要的是,，在人肺腺癌組織中，TIP30蛋白低表達(dá)與病人整體生存時(shí)間的延長(zhǎng)成正相關(guān)性,。
總之,，這些結(jié)果表明TIP30蛋白作為一種腫瘤抑制基因，抑制表皮生長(zhǎng)因子受體細(xì)胞質(zhì)和核信號(hào),，抑制肺腺腫瘤組織中血管生成,，降低TIP30蛋白表達(dá)靶向抑制EGFR信號(hào)可能是肺腺癌患者一種新的治療策略。（生物谷：Bioon.com）
doi:10.1038/onc.2012.253
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TIP30 loss enhances cytoplasmic and nuclear EGFR signaling and promotes lung adenocarcinogenesis in mice.
Li A, Zhang C, Gao S, Chen F, Yang C, Luo R, Xiao H.
Lung adenocarcinoma, the most common type of human non-small cell lung cancer (NSCLC), frequently overexpresses epidermal growth factor receptor (EGFR). However, the mechanisms underlying EGFR overexpression are not completely understood. Recent studies have identified that decreased expression of TIP30 (30kDa HIV-1 Tat interacting protein) is associated with the metastasis of human NSCLCs, but a causative relationship between TIP30 deficiency and NSCLC development remains unclear. We show here that Tip30 deletion leads to spontaneous development of lung adenomas and adenocarcinomas in mice. Lung tumor development was preceded by aberrant expansion of bronchioalveolar stem/progenitor and alveolar type II (AT2) cells, and also increased expression of EGFR and its downstream signaling factors in the lung of Tip30(-/-) mice. Moreover, TIP30 knockdown in human lung adenocarcinoma cells resulted in prolonged EGFR activity in early endosomes, delayed EGFR degradation, increased EGFR nuclear localization, leading to upregulated pAKT and pERK1/2 expression. Importantly, in human lung adenocarcinomas, low TIP30 expression correlates with prolonged patient overall and post-progression survival times. Together, these results suggest that TIP30 functions as a tumor suppressor to inhibit EGFR cytoplasmic and nuclear signaling and suppress adenocarcinogenesis in the lung, and highlight the potential of therapeutic strategies aiming at inhibiting EGFR signaling for patients with low TIP30-expression lung adenocarcinoma.
