Molecular mechanisms of Hippo pathway in tumorigenesis: therapeutic implications

被引：1

作者：

Saadh, Mohamed J. ^{[1
]}

Ahmed, Hanan Hassan ^{[2
]}

Kareem, Radhwan Abdul ^{[3
]}

Bishoyi, Ashok Kumar ^{[4
]}

Roopashree, R. ^{[5
]}

Shit, Debasish ^{[6
]}

Arya, Renu ^{[7
]}

Sharma, Abhishek ^{[8
]}

Khaitov, Kakhramon ^{[9
]}

Sameer, Hayder Naji ^{[10
]}

Yaseen, Ahmed ^{[11
]}

Athab, Zainab H. ^{[12
]}

Adil, Mohaned ^{[13
]}

机构：

[1] Middle East Univ, Fac Pharm, Amman 11831, Jordan

[2] Alnoor Univ, Coll Pharm, Mosul, Iraq

[3] Ahl Al Bayt Univ, Kerbala, Iraq

[4] Marwadi Univ, Res Ctr, Fac Sci, Dept Microbiol, Rajkot 360003, Gujarat, India

[5] JAIN, Sch Sci, Dept Chem & Biochem, Bangalore, Karnataka, India

[6] Chitkara Univ, Inst Engn & Technol, Ctr Res Impact & Outcome, Rajpura 140401, Punjab, India

[7] Chandigarh Grp Coll Jhanjeri, Chandigarh Pharm Coll, Dept Pharm, Mohali 140307, Punjab, India

[8] Nims Univ Rajasthan, Natl Inst Med Sci, Dept Med, Jaipur, India

[9] Tashkent Pediat Med Inst, Dept Oncol Pediat Oncol, 223 Bogishamol St, Tashkent 100140, Uzbekistan

[10] Natl Univ Sci & Technol, Coll Pharm, Dhi Qar 64001, Iraq

[11] Gilgamesh Ahliya Univ, Baghdad, Iraq

[12] Al Zahrawi Univ Coll, Dept Pharm, Karbala, Iraq

[13] Al Farahidi Univ, Pharm Coll, Baghdad, Iraq

来源：

MOLECULAR BIOLOGY REPORTS | 2025年 / 52卷 / 01期

关键词：

Hippo signaling; YAP; TAZ; Regulation; Tumorigenesis; Cancer therapy; YAP SIGNALING PATHWAY; ORGAN SIZE CONTROL; PROMOTER HYPERMETHYLATION; CONTACT INHIBITION; YAP/TAZ; CANCER; EXPRESSION; TARGETS; TEAD; ASSOCIATION;

D O I：

10.1007/s11033-025-10372-y

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The Hippo signaling pathway is a pivotal regulator of tissue homeostasis, organ size, and cell proliferation. Its dysregulation is profoundly implicated in various forms of cancer, making it a highly promising target for therapeutic intervention. This review extensively evaluates the mechanisms underlying the dysregulation of the Hippo pathway in cancer cells and the molecular processes linking these alterations to tumorigenesis. Under normal physiological conditions, the Hippo pathway is a guardian, ensuring controlled cellular proliferation and programmed cell death. However, numerous mutations and epigenetic modifications can disrupt this equilibrium in cancer cells, leading to unchecked cell proliferation, enhanced survival, and metastatic capabilities. The pathway's interaction with other critical signaling networks, including Wnt/beta-catenin, PI3K/Akt, TGF-beta/SMAD, and EGFR pathways, further amplifies its oncogenic potential. Central to these disruptions is the activation of YAP and TAZ transcriptional coactivators, which drive the expression of genes that promote oncogenesis. This review delves into the molecular mechanisms responsible for the dysregulation of the Hippo pathway in cancer, elucidating how these disruptions contribute to tumorigenesis. We also explore potential therapeutic strategies, including inhibitors targeting YAP/TAZ activity and modulators of upstream signaling components. Despite significant advancements in understanding the Hippo pathway's role in cancer, numerous questions remain unresolved. Continued research is imperative to unravel the complex interactions within this pathway and to develop innovative and effective therapies for clinical application. In conclusion, the comprehensive understanding of the Hippo pathway's regulatory mechanisms offers significant potential for advancing cancer therapies, regenerative medicine, and treatments for chronic diseases. The translation of these insights into clinical practice will necessitate collaborative efforts from researchers, clinicians, and pharmaceutical developers to bring novel and effective therapies to patients, ultimately improving clinical outcomes and advancing the field of oncology.

引用

页数：17

共 131 条

[1] Hippo pathway effectors YAP, TAZ and TEAD are associated with EMT master regulators ZEB, Snail and with aggressive phenotype in phyllodes breast tumors [J].