肥壮促癌又被证实!Cell 子刊:脂肪酸摄取失衡是癌症转移「罪魁祸首」
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;">【引入】</strong></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">俗话说一胖「毁」所有。<span style="color: black;">海量</span><span style="color: black;">科研</span><span style="color: black;">显示</span><span style="color: black;">肥壮</span>和<span style="color: black;">过重</span>与多种<span style="color: black;">疾患</span>密切<span style="color: black;">关联</span>。最新一项超 260 万人的随访<span style="color: black;">科研</span>,再次证明<span style="color: black;">肥壮</span>/<span style="color: black;">过重</span>与 18 种癌症密切<span style="color: black;">关联</span>,<strong style="color: blue;">BMI 越高,患癌<span style="color: black;">危害</span>以及患癌的死亡<span style="color: black;">危害</span>越高</strong>。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">肥壮</span>促进癌症<span style="color: black;">出现</span>的<span style="color: black;">原由</span><span style="color: black;">安在</span>?</strong><span style="color: black;">近期</span>,代谢<span style="color: black;">行业</span>顶刊 <strong style="color: blue;">Cell metabolism</strong><span style="color: black;">发布</span>最新<span style="color: black;">科研</span> CD36 maintains lipid homeostasis via selective uptake of monounsaturated fatty acids during matrix detachment and tumor progression,提出了<strong style="color: blue;">高脂<span style="color: black;">膳食</span>驱动的癌症转移新机制</strong>。<span style="color: black;">科研</span>发现<strong style="color: blue;">CD36 的表达受到 AMPK 和 p38 MAPK 激酶的严格调控</strong>,而榈酰化的 CD36 能够感知脂质饱和度,促进单不饱和脂肪酸的摄取,<span style="color: black;">从而</span>驱动高脂<span style="color: black;">膳食</span>时的乳腺癌转移。<strong style="color: blue;">为癌症转移的预防和治疗<span style="color: black;">供给</span>新的思路</strong>(<span style="color: black;">文末 p38 磷酸化抗体免费试用</span>)。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;">一</strong></p><span style="color: black;">
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;">MAPK 家族简介</strong></p>
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<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">癌症的<span style="color: black;">出现</span>发展或转移与多种激酶信号通路<span style="color: black;">相关</span>。<span style="color: black;">以上</span><span style="color: black;">科研</span>中的 p38 激酶属于 MAPK(丝裂原活化蛋白激酶)家族。MAPK 信号通路调节与癌症发展<span style="color: black;">关联</span>的一系列细胞过程,<span style="color: black;">包含</span>增殖、分化、凋亡、炎症和免疫等。MAPK 信号传导<span style="color: black;">反常</span>可能<span style="color: black;">引起</span>细胞增殖过度或失调,以及对细胞凋亡的抵抗。<strong style="color: blue;">p38 连同 ERK,JNK 被认为是致癌中发挥<span style="color: black;">功效</span>的三大 MAPK。</strong></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;">二</strong></p><span style="color: black;">
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;">p38 MAPK:信号转导枢纽</strong></p>
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<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">p38 MAPK 最初被确定为一种磷酸化不同转录因子的应激反应蛋白激酶。激酶结构域中部存在保守序列 TGY,其中 180 位苏氨酸 T(p38γ 为 183 位)及 182 位酪氨酸 Y(p38γ 为 185 位)可被 MKK3/4、TAK1 等磷酸化。<strong style="color: blue;">被活化磷酸化后<span style="color: black;">起步</span>下游一系列信号转导,并差异性改变下游多种蛋白的活性状态,如转录因子,细胞骨架蛋白,胞质蛋白和其它激酶等</strong>,其中激酶 MAPKAPK2 是典型的 p38 MAPK 激酶底物。<strong style="color: blue;">p38 MAPK 的激活<span style="color: black;">亦</span>可直接影响基因的转录</strong>,如 ATF1,2 和 SAP1 等。<span style="color: black;">另外</span>,p38 MAPK 激酶的<span style="color: black;">另一</span>一个<span style="color: black;">要紧</span>靶点是肿瘤<span style="color: black;">控制</span>蛋白 p53,其激活受到 p38 的正调控。<span style="color: black;">因此呢</span>,p38 MAPK 信号通路对细胞生理代谢和机体稳态的维持至关<span style="color: black;">要紧</span>。p38 信号通路的失调,尤其是 p38γ,与癌症的发展、转移、自噬和肿瘤微环境等密切<span style="color: black;">关联</span>。</p><img src="https://mmbiz.qpic.cn/sz_mmbiz_png/DvmRKVEib8McOQxTEc6ZDrMXd2znyhPJYgCEMKk2IdGpac6YRF5y9TZNlnFZhzJvb4B21jkyWMiag4HAnmXCy6yw/640?wx_fmt=png&from=appmsg&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;">
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">图 1. p38 MAPK 家族分布。p38 MARK 家族<span style="color: black;">包含</span>四个亚型:p38α(MAPK14)、p38β(MAPK11)、p38γ(MAPK12)和 p38δ(MAPK13),整体序列同源性 > 60%,激酶域内的同一性 > 90%。在<span style="color: black;">各样</span>组织中以不同的亚型<span style="color: black;">广泛</span>表达。p38α 在几乎所有类型细胞中表达,而 p38β <span style="color: black;">重点</span>在脑组织中表达,p38γ <span style="color: black;">重点</span>在骨骼肌中表达,p38δ <span style="color: black;">重点</span>在肾等组织中表达。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;">三</strong></p><span style="color: black;">
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;">p38 MAPK:癌症治疗靶点</strong></p>
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<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;">在不同的癌症、癌症的不同<span style="color: black;">周期</span>中,p38 扮演者不同的角色。</strong>在癌症<span style="color: black;">初期</span>,有<span style="color: black;">科研</span><span style="color: black;">显示</span> p38 能够<span style="color: black;">经过</span>调控细胞周期、细胞凋亡<span style="color: black;">控制</span>癌症。而在癌症晚期,部分<span style="color: black;">科研</span><span style="color: black;">显示</span> p38 能够<span style="color: black;">加强</span>肿瘤迁移能力,<span style="color: black;">加强</span>抗肿瘤药的耐药性。这种多变的表现可能是<span style="color: black;">因为</span> p38 能够调控<span style="color: black;">海量</span>不同底物(p38 的底物超过两百种),不同信号通路之间又存在着<span style="color: black;">繁杂</span>的 crosstalk。<strong style="color: blue;">越来越多<span style="color: black;">科研</span><span style="color: black;">显示</span> p38 可<span style="color: black;">做为</span>癌症的治疗靶点。</strong><span style="color: black;">控制</span> p38γ 的表达,<span style="color: black;">能够</span>阻止裸鼠<span style="color: black;">身体</span>食管鳞状细胞癌(ESCC)<span style="color: black;">发展</span>;ERK1/2 和 p38 激酶与胃癌耐药性<span style="color: black;">加强</span><span style="color: black;">相关</span>;<strong style="color: blue;">p38γ <span style="color: black;">亦</span>可<span style="color: black;">做为</span>结直肠癌和肝癌的治疗靶点</strong>。有<span style="color: black;">科研</span><span style="color: black;">表示</span><strong style="color: blue;">靶向失活 p38α 可<span style="color: black;">做为</span>辅助治疗<span style="color: black;">控制</span>黑色素瘤的肺转移</strong>。</p><img src="https://mmbiz.qpic.cn/sz_mmbiz_png/DvmRKVEib8McOQxTEc6ZDrMXd2znyhPJYW2TFddJ3ibIkJ9xCPRuzV0uaOUQEMpiaqAeMVzNlddnTZgzSbwm89eZw/640?wx_fmt=png&from=appmsg&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;">
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">图 2. P38 在肿瘤进程中的双面性</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">日前</span>关于p38的<span style="color: black;">药品</span><span style="color: black;">开发</span><span style="color: black;">重点</span>集中在小分子<span style="color: black;">控制</span>中,但<span style="color: black;">日前</span>尚<span style="color: black;">没</span>成功<span style="color: black;">药品</span>,一个<span style="color: black;">要紧</span>的<span style="color: black;">原由</span><span style="color: black;">便是</span><span style="color: black;">针对</span>p38的<span style="color: black;">繁杂</span>调控<span style="color: black;">认识</span>尚少。<strong style="color: blue;"><span style="color: black;">因此呢</span>加深对p38的了解,尤其是磷酸化动态调控<span style="color: black;">非常</span>必要。p38磷酸化的有效检测<span style="color: black;">作为</span><span style="color: black;">科研</span>的重中之重!</strong></p>
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<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">扫码申请试用<img src="https://res.wx.qq.com/t/wx_fed/we-emoji/res/v1.3.10/assets/Expression/Expression_85@2x.png?tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;"></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="https://mmbiz.qpic.cn/sz_mmbiz_png/DvmRKVEib8McOQxTEc6ZDrMXd2znyhPJYkpJ8MgTvugMUweRv52EGMPBUakUHbnEIh61spMJibsvjshy9otyqkyw/640?wx_fmt=png&from=appmsg&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;"></p><img src="https://mmbiz.qpic.cn/sz_mmbiz_png/DvmRKVEib8McOQxTEc6ZDrMXd2znyhPJY6Yx6eLJq39dqAuH8QXUGEicHdTILriatQFEHLndyllsFcL3M1icPSTwPA/640?wx_fmt=png&from=appmsg&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;">
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;">展示数据:</strong></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">WB 应用(多肽竞争特异性验证)</p><img src="https://mmbiz.qpic.cn/sz_mmbiz_png/DvmRKVEib8McOQxTEc6ZDrMXd2znyhPJYycsGw1PoictbRwSh5EP9okvnjmwbVlye3o8ribpLJ1ic7bIiahCkgfUb4Q/640?wx_fmt=png&from=appmsg&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;">
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">图 3. Western blot analysis of extracts from serum-starved NIH-3T3, untreated (line A); treated with UV (30 min), without peptide (line B) or antigen-specific phosphopeptide (line C) or antigen-specific peptide (line D) using Phospho-p38 MAPK (Thr180, Tyr182) rabbit monoclonal Antibody (Cat# 110435-R0004) at 1:1000 dilution.</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">IHC 应用(磷酸酶特异性验证)</p><img src="https://mmbiz.qpic.cn/sz_mmbiz_png/DvmRKVEib8McOQxTEc6ZDrMXd2znyhPJYySTq2icNIKpFElduJZ6EBzAcFtJPicl0ibEUiaHpSAYRjnDluInEy3oDJg/640?wx_fmt=png&from=appmsg&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;">
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">图 4. Immunohistochemical analysis of paraffin-embedded human carcinoma of sigmoid tissue,untreated (left) or lambda phosphatase-treated (right), using Recombinant Phospho-p38 MAPK (Thr180-Tyr182) Antibody, Rabbit Monoclonal (Cat# 110435-R0004) at 1:500 dilution.</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">IF 应用(磷酸酶特异性验证)</p><img src="https://mmbiz.qpic.cn/sz_mmbiz_jpg/DvmRKVEib8McOQxTEc6ZDrMXd2znyhPJYIIJn1zIJRVBhNCicc4hcvrT0ppmHUOPMmlC0fPSq5F1aUBk9Vib4L9ow/640?wx_fmt=jpeg&from=appmsg&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;">
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">图 5. Immunofluorescence staining of Phospho-p38 MAPK (Thr180, Tyr182) in serum-starved NIH-3T3 cells, untreated (left), treated with UV (30mins) (middle) or treated with UV (30mins) and lambda phosphatase (right). Cells were fixed with 4% PFA, permeabilzed with 0.1% Triton X-100 in PBS, blocked with 10% serum, and incubated with rabbit anti-Mouse Phospho-p38 MAPK (Thr180, Tyr182) monoclonal antibody (dilution ratio 1:60) at 4℃ overnight. Then cells were stained with the Alexa Fluor®488-conjugated Goat Anti-rabbit IgG secondary antibody (green). Positive staining was mainly localized to Nucleus.</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">稳定性测试(加速实验)</p><img src="https://mmbiz.qpic.cn/sz_mmbiz_png/DvmRKVEib8McOQxTEc6ZDrMXd2znyhPJYdXEufCVNZrCWsLqCibtVia7pPF5nE8dPJT5Chn4CvMr1I8kvibNym4MDw/640?wx_fmt=png&from=appmsg&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;">
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">图 6. Recombinant Phospho-p38 MAPK (Thr180, Tyr182) Antibody, Rabbit Monoclonal (Cat: 110435-R0004) was placed in 25℃ for 8 days, in 25℃ for 16 days, in 37℃ for 3.5 days, in 37℃ for 7 days respectively. The cell lysates were serum-starved NIH-3T3, untreated or treated with UV (30 min). The antibody after accelerated by different temperature still showed significant specificity.</p><img src="https://mmbiz.qpic.cn/mmbiz_svg/hIz3ylFIYSicERH8wXibRqsVrztU8CiaHyRMtAkHXlX6OYvaNCr7GAFN5xme93yTB8qlUsgicK6URoS3sX1NwELxLsqIbSo74srt/640?wx_fmt=svg&from=appmsg&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;">
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<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">内容策划:王丹琦</p>内容审核:周育红
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">题图<span style="color: black;">源自</span>:图虫创意</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;">参考文献:</strong></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">. Recalde M, Pistillo A, Davila-Batista V, et al. Longitudinal body mass index and cancer risk: a cohort study of 2.6 million Catalan adults. Nat Commun. 2023 Jun 30;14(1):3816. doi: 10.1038/s41467-023-39282-y.</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">. Terry AR, Nogueira V, Rho H, et al. CD36 maintains lipid homeostasis via selective uptake of monounsaturated fatty acids during matrix detachment and tumor progression. Cell Metab. 2023 Nov 7;35(11):2060-2076.e9. doi: 10.1016/j.cmet.2023.09.012.</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">. García-Hernández, L., García-Ortega, M. B., Ruiz-Alcalá, G., Carrillo, E., Marchal, J. A., & García, M. (2021). The p38 MAPK Components and Modulators as Biomarkers and Molecular Targets in Cancer. Int J Mol Sci, 23(1). https://doi.org/10.3390/ijms23010370</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">. Martínez-Limón, A., Joaquin, M., Caballero, M., Posas, F., & de Nadal, E. (2020). The p38 Pathway: From Biology to Cancer Therapy. Int J Mol Sci, 21(6). https://doi.org/10.3390/ijms21061913</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">. Thuy Phan, et al. P38 kinase in gastrointestinal cancers. Cancer Gene Therapy (2023)</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">. Gui J, Zahedi F, Ortiz A, et al. Activation of p38α stress-activated protein kinase drives the formation of the pre-metastatic niche in the lungs. Nat Cancer. 2020 Jun;1(6):603-619. doi: 10.1038/s43018-020-0064-0.</p>
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