TGF-I3 signaling pathway: Therapeutic targeting and potential for anti-cancer immunity

被引:34
作者
Ali, Shafat [1 ,2 ,3 ]
Rehman, Muneeb U. [4 ]
Yatoo, Ali Mohd [1 ]
Arafah, Azher [4 ]
Khan, Andleeb [5 ]
Rashid, Summya [6 ]
Majid, Sabhiya [2 ]
Ali, Aarif [7 ]
Ali, Md. Niamat [1 ]
机构
[1] Univ Kashmir, Ctr Res Dev, Cytogenet & Mol Biol Lab, Srinagar 190006, Jammu & Kashmir, India
[2] Govt Med Coll, Dept Biochem, Srinagar 190010, Jammu & Kashmir, India
[3] Govt Med Coll, Multidisciplinary Res Unit MRU, Srinagar 190010, Jammu & Kashmir, India
[4] King Saud Univ, Coll Pharm, Dept Clin Pharm, Riyadh 11451, Saudi Arabia
[5] Jazan Univ, Coll Pharm, Dept Pharmacol & Toxicol, Jazan 45142, Saudi Arabia
[6] Prince Sattam Bin Abdulaziz Univ, Coll Pharm, Dept Pharmacol & Toxicol, Al Kharj 11942, Saudi Arabia
[7] Sher E Kashmir Univ Agr Sci & Technol Kashmir SKUA, Fac Vet Sci & Anim Husb, Div Vet Biochem, Shuhama Campus Alusteng, Ganderbal 190006, Jammu & Kashmir, India
关键词
TGFI3; Tumorigenesis; Tumor microenvironment; Immune-suppression; Kinase-inhibitors; Antibodies; Anti-sense oligonucleotides; GROWTH-FACTOR-BETA; RECEPTOR-TYPE-II; BREAST-CANCER PROGRESSION; EPITHELIAL-MESENCHYMAL TRANSITION; SQUAMOUS-CELL CARCINOMA; PRIMARY TUMOR-GROWTH; KINASE INHIBITOR; PHASE-I; COLON-CANCER; HEPATOCELLULAR-CARCINOMA;
D O I
10.1016/j.ejphar.2023.175678
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Transforming growth factor-I3 (TGFI3) is a pleiotropic secretory cytokine exhibiting both cancer-inhibitory and promoting properties. It transmits its signals via Suppressor of Mother against Decapentaplegic (SMAD) and nonSMAD pathways and regulates cell proliferation, differentiation, invasion, migration, and apoptosis. In noncancer and early-stage cancer cells, TGFI3 signaling suppresses cancer progression via inducing apoptosis, cell cycle arrest, or anti-proliferation, and promoting cell differentiation. On the other hand, TGFI3 may also act as an oncogene in advanced stages of tumors, wherein it develops immune-suppressive tumor microenvironments and induces the proliferation of cancer cells, invasion, angiogenesis, tumorigenesis, and metastasis. Higher TGFI3 expression leads to the instigation and development of cancer. Therefore, suppressing TGFI3 signals may present a potential treatment option for inhibiting tumorigenesis and metastasis. Different inhibitory molecules, including ligand traps, anti-sense oligo-nucleotides, small molecule receptor-kinase inhibitors, small molecule inhibitors, and vaccines, have been developed and clinically trialed for blocking the TGFI3 signaling pathway. These molecules are not pro-oncogenic response-specific but block all signaling effects induced by TGFI3. Nonetheless, targeting the activation of TGFI3 signaling with maximized specificity and minimized toxicity can enhance the efficacy of therapeutic approaches against this signaling pathway. The molecules that are used to target TGFI3 are non-cytotoxic to cancer cells but designed to curtail the over-activation of invasion and metastasis driving TGFI3 signaling in stromal and cancer cells. Here, we discussed the critical role of TGFI3 in tumorigenesis, and metastasis, as well as the outcome and the promising achievement of TGFI3 inhibitory molecules in the treatment of cancer.
引用
收藏
页数:24
相关论文
共 388 条
[1]   TGF-β signaling in cancer -: a double-edged sword [J].
Akhurst, RJ ;
Derynck, R .
TRENDS IN CELL BIOLOGY, 2001, 11 (11) :S44-S51
[2]   Targeting TGF-β Signaling for Therapeutic Gain [J].
Akhurst, Rosemary J. .
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, 2017, 9 (10)
[3]   Targeting the TGFβ signalling pathway in disease [J].
Akhurst, Rosemary J. ;
Hata, Akiko .
NATURE REVIEWS DRUG DISCOVERY, 2012, 11 (10) :790-811
[4]   The TGFβ pathway stimulates ovarian cancer cell proliferation by increasing IGF1R levels [J].
Alsina-Sanchis, Elisenda ;
Figueras, Agnes ;
Lahiguera, Alvaro ;
Vidal, August ;
Casanovas, Oriol ;
Graupera, Mariona ;
Villanueva, Alberto ;
Vinals, Francesc .
INTERNATIONAL JOURNAL OF CANCER, 2016, 139 (08) :1894-1903
[5]   Tissue-wide expression profiling using cDNA subtraction and microarrays to identify tumor-specific genes [J].
Amatschek, S ;
Koenig, U ;
Auer, H ;
Steinlein, P ;
Pacher, M ;
Gruenfelder, A ;
Dekan, G ;
Vogl, S ;
Kubista, E ;
Heider, KH ;
Stratowa, C ;
Schreiber, M ;
Sommergruber, W .
CANCER RESEARCH, 2004, 64 (03) :844-856
[6]  
An H.W., 2021, P C KOR SOC EXP AN R, V2021, P213
[7]   BMP-1 disrupts cell adhesion and enhances TGF-β activation through cleavage of the matricellular protein thrombospondin-1 [J].
Anastasi, Cyril ;
Rousselle, Patricia ;
Talantikite, Maya ;
Tessier, Agnes ;
Cluzel, Caroline ;
Bachmann, Alice ;
Mariano, Natacha ;
Dussoyer, Melissa ;
Alcaraz, Lindsay B. ;
Fortin, Laetitia ;
Aubert, Alexandre ;
Delolme, Frederic ;
El Kholti, Naima ;
Armengaud, Jean ;
Fournie, Pierre ;
Auxenfans, Celine ;
Valcourt, Ulrich ;
Vadon-Le Goff, Sandrine ;
Moali, Catherine .
SCIENCE SIGNALING, 2020, 13 (639)
[8]  
Anderson Cancer Center (ACC), 2018, M7824 TREAT PAT STAG
[9]  
Andreasen PA, 1997, INT J CANCER, V72, P1, DOI 10.1002/(SICI)1097-0215(19970703)72:1<1::AID-IJC1>3.0.CO
[10]  
2-Z