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结直肠癌 - EnkiLife


结直肠癌(CRC)

结直肠癌 (CRC) 是第三常见的癌症和第二大致死率的癌症。其复杂性受到多种信号转导网络的影响，这些 网络管理细胞增殖、存活、分化和凋亡。CRC的发病机制核心在于驱动肿瘤形成的异常信号通路，维持癌细胞增殖，并使转移扩散得以实现[1]。这些通路包括Wnt/β-连环蛋白、RAS/RAF/MEK/ERK、PI3K/AKT和TGF-β回路等。本文旨在解析与CRC相关的信号机制，以阐明肿瘤进化和进展的一般原则[2]。

一、结直肠癌发生中涉及的多种信号级联反应

CRC是由几种关键信号通路的失调驱动的，这些信号通路集体促进了在肿瘤发生过程中获得的标志性能力。包括Wnt、IGF2、ErbB、TGF-β、Notch、Hedgehog和TNFα途径(图1)。其详细说明了细胞外信号如何通过受体和细胞内分子传递到细胞核，强调了这些信号网络在结直肠癌的发展和进展中的复杂性和相互关联性[2]。

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二、E3 泛素连接酶对结直肠癌的影响

E3 泛素连接酶在结直肠癌的启动和进展中起着至关重要的作用，一些E3 泛素连接酶通过促进癌基因的降解作为肿瘤抑制因子，而另一些则通过抑制肿瘤抑制因子的降解或促进代谢开关的降解作为癌基因因子自身发挥作用（图2）。它们通过标记底物蛋白进行泛素化，并随后降解信号通路中的关键蛋白。通过调节泛素化和降解过程，E3 泛素连接酶可以作为肿瘤发生的促进剂或抑制剂[3]。

三、UPS和自噬-溶酶体途径在CRC中的双重作用

除了E3连接酶，过去二十年中UPS一直是靶向蛋白质降解（TPD）疗法的目标 [4]。靶向蛋白降解已经成为治疗包括结直肠癌（CRC）在内的癌症的一种有前途的方法（图3）。UPS和自噬-溶酶体途径之间的复杂相互作用需要进一步探索，未来的研究应重点理解多种蛋白质降解途径在CRC治疗中的共同作用[3]。

四、铁死亡在结直肠癌中的作用

CRC与其他癌症相比，与铁死亡的关系更密切。首先，由于胃肠道的特殊环境，TFRC在结直肠癌中过表达，其次，结直肠癌是唯一维持铁摄取来源的恶性肿瘤，这导致细胞中存在过量的铁，从而更容易发生铁死亡 [5]。此外，CRC细胞中的ROS含量通常高于其他正常细胞。因此，ROS可能会在不影响正常细胞的情况下诱导癌细胞发生铁死亡（图4）。由此可见，理解铁死亡在CRC中的作用及其调控机制在CRC的治疗中起着至关重要的作用[6]。

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五、铜和铜死亡在结直肠癌中的作用

最近的研究发现，CRC 组织和患者血清中的铜水平（主要通过血浆 CP 水平检测）高于健康个体，表明铜在CRC发展和细胞增殖中起着重要作用[7]。此外，升高的铜水平对其转移也至关重要，特别是转移到肝脏，肝脏是远处CRC转移的最常见部位和铜的储存器官[8]。最近的研究表明，CRC肝转移中的铜水平显著高于正常肝组织中的铜水平[9]。总之，铜和铜结合蛋白与结直肠癌的增殖和转移密不可分（图5），这使得靶向铜离子成为CRC的一种有前景的治疗方法[10]。

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结直肠癌相关抗体：
TargetCatalog#Product NameReactivityApplication
结直肠癌发生中的多种信号级联反应相关抗体：
CK1AMM80556CK1 Mouse Monoclonal AntibodyHumanIHC,ELISA
APCAMM81364APC Mouse Monoclonal AntibodyHumanFC,ELISA
AXIN1AMM81858AXIN1 Mouse Monoclonal AntibodyHumanICC,FC,ELISA
MVP/LRPAMRe02292MVP Rabbit Monoclonal AntibodyHumanWB,IHC-F,IHC-P,ICC/IF
CTNNB1AMM80788CTNNB1 Mouse Monoclonal AntibodyHumanIHC,ICC,FC,ELISA
P300/CBPAMRe86527P300/CBP Rabbit Monoclonal AntibodyHuman,Mouse,RatWB, ICC/IF, FC, IP
TCF7AMRe21151TCF7 Rabbit Monoclonal antibodyHuman,RatWB,IHC,IF,IP,ELISA
TGFβ1 / TGFBAMM81164IGF2 Mouse Monoclonal AntibodyHumanIHC,ICC,FC,ELISA
IGFR1/CD64AMM82073CD64 Mouse Monoclonal AntibodyHumanIHC,FC,ELISA
IRS2APRab12761IRS2 Rabbit Polyclonal AntibodyHuman,MouseWB,ELISA
AKTAMRe03759AKT Rabbit Monoclonal AntibodyHuman,Mouse,Rat,HamsterWB,IHC-F,IHC-P,ICC/IF,IP
BadAMRe21496Bad Rabbit Monoclonal antibodyHuman,Mouse,RatWB,IHC,IF,IP,ELISA
Bcl-XLAMRe04056Bcl-XL Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC-F,IHC-P,ICC/IF,IP
MDM2AMM81436MDM2 Mouse Monoclonal AntibodyHumanFC,ELISA
ATMAMRe01480ATM Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,ICC/IF
p21AMRe86606p21 Rabbit Monoclonal AntibodyHumanWB, IHC-P, ICC/IF, FC, IP
mTORAMM81583mTOR Mouse Monoclonal AntibodyHuman,Mouse,Rat,RabbitIHC,ELISA
ErbB 2AMRe86308ErbB 2 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB, IHC-P, ICC/IF, FC, IP
ErbB-3AMRe21268ErbB-3 Rabbit Monoclonal antibodyHuman,Mouse,RatWB,IF,IP,ELISA
ErbB 4AMRe86975ErbB 4 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB, FC
GRB2AMRe86265GRB2 Rabbit Monoclonal AntibodyHuman, Mouse, RatWB,IHC,ICC/IF,IP
SOS1AMRe83936SOS1 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC,IF
RasAMRe83897Ras Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IP,IHC,ICC,FC,IF
Raf-1/RAFAMRe21114Raf-1 Rabbit Monoclonal antibodyHuman,Mouse,RatWB,IF,IP,ELISA
MEK7/MEKAMRe86956MEK7 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC-P,FC
ERK2/ERKAMRe01524ERK2 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC-F,IHC-P,ICC/IF,IP
MYCAMM82414MYC Mouse Monoclonal AntibodyHumanFC,ELISA
TGF beta 1AMM84982TGF beta 1 Mouse Monoclonal AntibodyHuman,Mouse,RatWB,IHC
TGFβ RIAPRab18855TGFβ RI Rabbit Polyclonal AntibodyHuman,Mouse,RatWB,IF-P,IF-F,ICC/IF,ELISA
TGFβ RIIAPRab18856TGFβ RII Rabbit Polyclonal AntibodyHuman,Mouse,RatIF-P,IF-F,ICC/IF,WB,IHC-P,ELISA
Smad2/3AMRe87734Smad2/3 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB, ICC/IF, FC, IP
Smad4AMRe03205Smad4 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,ICC/IF,IP
AMPK alpha 1AMRe86460AMPK alpha 1 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB, IHC-P, ICC/IF, FC, IP
FASNAMRe10839FASN (17A14) Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,ICC/IF,FC
p53AMRe02387p53 Rabbit Monoclonal AntibodyHumanWB,ICC/IF
p21AMRe21315p21 Rabbit Monoclonal antibodyMouse,RatWB,IHC,IF,IP,ELISA
PTCH1/PTCHAPRab00420PTCH1 Rabbit Polyclonal AntibodyHuman,MouseWB,IHC-P,ELISA
SmoAPRab18026Smo Rabbit Polyclonal AntibodyHuman,Mouse,RatWB,ELISA
SUFUAMRe86597SUFU Rabbit Monoclonal AntibodyHuman,Mouse,RatWB, FC
GLI1AMM81512GLI1 Mouse Monoclonal AntibodyHumanIHC,ICC,FC,ELISA
GLI2AMM83347GLI2 Mouse Monoclonal AntibodyHumanIHC
GLI3AMRe02036GLI3 Rabbit Monoclonal AntibodyHumanWB,ICC/IF
GSK3BAMM80814GSK3B Mouse Monoclonal AntibodyHuman,Mouse,Rat,MonkeyWB,IHC,ICC,FC,ELISA
MST1AMRe02805MST1 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC-P
STK3AMRe02643STK3 Rabbit Monoclonal AntibodyHuman,Mouse,Rat,HamsterWB,IHC-P,IP
LATS1/2APRab13235LATS1/2 Rabbit Polyclonal AntibodyHuman,MouseWB,IHC-P,IF-P,IF-F,ICC/IF,ELISA
YAPAMRe21335YAP Rabbit Monoclonal antibodyHuman,Mouse,RatWB,IHC,IF,IP,ELISA
TNF αAMRe21365TNF α Rabbit Monoclonal antibodyHuman,Mouse,RatWB,IHC,IF,IP,ELISA
TAK1AMRe02664TAK1 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC-F,IHC-P,ICC/IF
FADDAMRe85554FADD Rabbit Monoclonal Antibody AntibodyHuman,MouseWB,IHC
IKB alphaAMRe01574IKB alpha Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC-P,IP
CASP8AMM85086Cleaved-Caspase 8 Mouse Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC
E3泛素连接酶在CRC进化中相关抗体：
RNF6AMM83194RNF6 Mouse Monoclonal AntibodyHumanIHC
UbAPRab19487Ub Rabbit Polyclonal AntibodyHuman,Mouse,RatIF-P,IF-F,ICC/IF,WB,IHC-P,ELISA
TCF4AMRe86541TCF4 Rabbit Monoclonal AntibodyHuman,MouseWB, IHC-P, FC
beta CateninAMRe03746beta Catenin Rabbit Monoclonal AntibodyHuman,Mouse,Rat,HamsterWB,IHC-P,IP
TRIM47AMM83488TRIM47 Mouse Monoclonal AntibodyHumanIHC
Smad4AMRe03205Smad4 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,ICC/IF,IP
CCL15AMM83184CCL15 Mouse Monoclonal AntibodyHuman, RatWB,IHC
CCR10AMM82596CCR10 Mouse Monoclonal AntibodyHumanIHC,ICC,FC,ELISA
PTENAMRe87301PTEN Rabbit Monoclonal AntibodyHuman,Mouse,RatWB, IHC-P, FC, IP
p53AMRe02387p53 Rabbit Monoclonal AntibodyHumanWB,ICC/IF
MLXIPL/CHREBPAMM81284MLXIPL Mouse Monoclonal AntibodyHumanICC,ELISA
eIF5AAMRe01587eIF5A Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC-P,IP
TEMTAMRe18787TEMT (3C18) Rabbit Monoclonal AntibodyHuman,Mouse,RatWB
NF-κB p65/p65AMM80783NF-κB p65 Mouse Monoclonal AntibodyHuman,Mouse,Rat,Rabbit,MonkeyWB,IHC,ELISA
UPS和自噬-溶酶体途径在CRC中的相关抗体：
UbAPRab19487Ub Rabbit Polyclonal AntibodyHuman,Mouse,RatIF-P,IF-F,ICC/IF,WB,IHC-P,ELISA
AMPKAMRe87445AMPK alpha 1/2 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB, IP
p-ULK1AMRe21107ULK1 (Phospho Ser757) Rabbit Monoclonal antibodyHuman,Mouse,RatWB,IF,IP,ELISA
p27APRab15594p27 Rabbit Polyclonal AntibodyHuman,Rat,Mouse,BovineWB,IHC-P,IF-P,IF-F,ICC/IF,ELISA
p53AMRe87631p53 Rabbit Monoclonal AntibodyHumanWB, IHC-P, ICC/IF, FC, IP
IκB-αAMRe21140IκB-α Rabbit Monoclonal antibodyHuman,Mouse,RatWB,IHC,IF,IP,ELISA
LC3APRab03870LC3A/B Rabbit Polyclonal AntibodyHuman,Mouse,RatWB
PIK3C3AMRe16090PI 3 Kinase Class 3 (11Y1) Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC-P,IF-P
ATG5AMRe21348ATG5 Rabbit Monoclonal antibodyHuman,Mouse,RatWB,IHC,IF,IP,ELISA
ATG7AMRe21471ATG7 Rabbit Monoclonal antibodyHuman,Mouse,RatWB,IHC,IF,IP,ELISA
CDKN1AAMM82580CDKN1A Mouse Monoclonal AntibodyHumanIHC,FC,ELISA
CCND1AMM82541CCND1 Mouse Monoclonal AntibodyHuman, MouseWB,IHC,FC,ELISA
p62AMRe03796SQSTM1/p62 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC-F,IHC-P,ICC/IF,IP
XIAPAMRe21157XIAP Rabbit Monoclonal antibodyHuman,Mouse,RatWB,IF,IP,ELISA
铁死亡在结直肠癌中的相关抗体：
xCT/SLC7A11AMRe83994xCT Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IP,ICC
SLC3A2/CD98AMRe08492CD98 (2G13) Rabbit Monoclonal AntibodyHumanWB,IHC-P,IP,IF-P
SCD1AMRe17641SCD1 (2W16) Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC-P,ICC/IF,FC,IP,IF-P
SREBP1APRab03400SREBP1 Rabbit Polyclonal AntibodyHuman,Mouse,RatWB,ELISA
ACSL4AMRe21426ACSL4 Rabbit Monoclonal antibodyHuman,Mouse,RatWB,IHC,IF,IP,ELISA
Nrf2AMRe21024Nrf2 Rabbit Monoclonal antibodyHuman,Mouse,RatWB,IHC,IF,IP,ELISA
Keap1AMRe21357Keap1 Rabbit Monoclonal antibodyHuman,Mouse,RatWB,IHC,IF,IP,ELISA
p53AMRe87631p53 Rabbit Monoclonal AntibodyHumanWB, IHC-P, ICC/IF, FC, IP
CDKN1AAMM82580CDKN1A Mouse Monoclonal AntibodyHumanIHC,FC,ELISA
GPX4AMRe21183GPX4 Rabbit Monoclonal antibodyHuman,Mouse,Rat,WB,IF,IP,ELISA
LOXAMRe86854LOX Rabbit Monoclonal AntibodyHuman,Mouse,RatWB, IHC-P, ICC/IF, FC, IP
AIFM2/FSP1APRab03391AIFM2/FSP1 Rabbit Polyclonal AntibodyHuman,Mouse,MonkeyWB,IHC-F,IHC-P,ICC/IF,ELISA
TFAPRab18809TF Rabbit Polyclonal AntibodyHuman,Rat,MouseWB,IHC-P,IF-P,IF-F,ICC/IF,ELISA
TFRCAMM81272TFRC Mouse Monoclonal AntibodyHuman,Mouse,Monkey,RatWB,ELISA
pHyde/STEAP3APRab16089pHyde Rabbit Polyclonal AntibodyHuman,Mouse,RatWB,IHC-P,IF-P,IF-F,ICC/IF,ELISA
CHMP2B/DMT1AMRe84605CHMP2B Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IP,ICC,FC
NCOA4AMM85928NCOA4(Ascites) Mouse Monoclonal AntibodyHumanWB
FTH1AMRe21408Ferritin Heavy Chain Rabbit Monoclonal antibodyHuman,Mouse,RatWB,IHC,IF,IP,ELISA
FTLAMM81367FTL Mouse Monoclonal AntibodyHumanWB,IHC,FC,ELISA
铜死亡在结直肠癌中的相关抗体：
LOXAMRe86854LOX Rabbit Monoclonal AntibodyHuman,Mouse,RatWB, IHC-P, ICC/IF, FC, IP
ATP7AAPRab07343ATP7A Rabbit Polyclonal AntibodyHuman,Mouse,RatIHC-P,IF-P,IF-F,ICC/IF,ELISA
CTR1/SLC31A1AMRe84671CTR1/SLC31A1 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB
VEGFA/VEGFAMRe21324VEGFA Rabbit Monoclonal antibodyHuman,Mouse,RatWB,IHC,IF,IP,ELISA
HIF-1-alphaAMRe12020HIF-1-alpha (9U11) Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,ICC/IF,IP
eNOSAMRe86625eNOS Rabbit Monoclonal AntibodyHuman,Mouse,RatWB, IP
HIF1AN/FIH-1/FIH1AMRe87233HIF1AN/FIH-1 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB, FC
FGF2/BFGFAMRe86980FGF2 Rabbit Monoclonal AntibodyHumanWB, IHC-P, IP
TNF αAMRe21365TNF α Rabbit Monoclonal antibodyHuman,Mouse,RatWB,IHC,IF,IP,ELISA
IL1 betaAMRe83698IL1 beta Rabbit Monoclonal AntibodyMouseWB,IP,FC
IL1AAMM82630IL1A Mouse Monoclonal AntibodyHumanICC,FC,ELISA
CCSAPRab08169CCS Rabbit Polyclonal AntibodyHuman,Rat,MouseWB,IHC-P,IF-P,IF-F,ICC/IF,ELISA
TEMTAMRe18787TEMT (3C18) Rabbit Monoclonal AntibodyHuman,Mouse,RatWB
p47-phoxAPRab15631p47-phox Rabbit Polyclonal AntibodyHuman,Mouse,RatWB,IHC-P,IF-P,IF-F,ICC/IF,ELISA
ATPAMM83010ATP Mouse Monoclonal AntibodyHumanFC,ELISA
ZEB1AMM81260ZEB1 Mouse Monoclonal AntibodyHumanIHC,ICC,FC,ELISA
SIP1/ZEB2APRab17905SIP1 Rabbit Polyclonal AntibodyHuman,Mouse,RatWB,IHC-P,IF-P,IF-F,ICC/IF,ELISA
STEAP4AMM83560STEAP4 Mouse Monoclonal AntibodyHumanIHC
XIAPAMRe21157XIAP Rabbit Monoclonal antibodyHuman,Mouse,RatWB,IF,IP,ELISA
Caspase 3AMRe01567Caspase 3 Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC-P,IP
Cyclin D1AMRe21529Cyclin D1 Rabbit Monoclonal antibodyHuman,Mouse,RatWB,IHC,IF,IP,ELISA
DLATAMRe84191DLAT Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IP,ICC,FC
FDX1/ADXAMRe84761FDX1/ADX Rabbit Monoclonal AntibodyHuman,Mouse,RatWB,IHC,ICC,IF
CD4AMRe21251CD4 Rabbit Monoclonal antibodyHuman,MouseWB,IHC,IF,IP,ELISA
CD8aAMM82375CD8a Mouse Monoclonal AntibodyHumanFC,ELISA


ELISA 试剂盒

TargetCatalog#Product NameReactivityDetection RangeSensitivity
Human TNFαEH10021Human TNF-α (Tumor Necrosis Factor Alpha) ELISA KitHuman7.81-500 pg/mL4.69 pg/mL
High Sensitivity Mouse TNFαEM27661SHigh Sensitivity Mouse TNF-α (Tumor Necrosis Factor Alpha) ELISA KitMouse1.56-100 pg/mL0.93 pg/mL
Mouse IL-1βEM27654SMouse IL-1β (Interleukin 1 Beta) ELISA KitMouse3.13-200 pg/mL1.87 pg/mL
Mouse IL-1αEM27657Mouse IL-1α (Interleukin 1 Alpha) ELISA KitMouse1.56-100 pg/mL0.47 pg/mL



参考文献

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    [3] Role of protein degradation systems in colorectal cancer. Cui, Z., et al. Cell Death Discov. 2024. [PMID: 38485957]

    [4] Targeted protein degradation: mechanisms, strategies and application. Zhao L, et al. Signal Transduct Target Ther. 2022. [PMID: 35379777]

    [5] Transferrin receptor-mediated iron uptake promotes colon tumorigenesis. Kim H, et al. Advanced Sci (Weinheim Baden-Wurttemberg Germany). 2023. [PMID: 36703617]

    [6] Research progress on ferroptosis in colorectal cancer. Front Immunol. Li Y, et al. 2024. [PMID: 39359721]

    [7] Blood copper levels and the occurrence of colorectal cancer in Poland. Baszuk P, et al. Biomedicines. 2021. [PMID: 34829856]

    [8] An evaluation study of trace element content in colorectal liver metastases and surrounding normal livers by X‐ray fluorescence. Gurusamy KS, et al. Biometals. 2008. [PMID: 18049861]

    [9] Copper in hepatocellular carcinoma: a double‐edged sword with therapeutic potentials. Wu Z, et al. Cancer Lett. 2023. [PMID: 37567461]

    [10] Copper in colorectal cancer: From copper-related mechanisms to clinical cancer therapies. Wang Y, et al. Clin Transl Med. 2024. [PMID: 38804588]


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