Hippo Tumor Suppressor Pathway is the main pathway for cell growth that regulates tissue enlargement and organ size by limiting cell growth. This pathway is activated in response to cell cycle arrest signals (cell polarity

transduction

and DNA damage) and limited by growth factors or mitogens associated with EGF and LPA. The major pathway consists of the central kinase of Ste20 MAPK (

Saccharomyces cerevisiae

)

Hpo (

Drosophila melanogaster

) or MST kinases (mammalian) that activates the mammalian AGC kinase

dm

Wts or LATS effector (MST and LATS). YAP in the nucleus work as a cofactor for a wide range of transcription factors involved in proliferation (TEA domain family

TEAD1-4)

stem cells (Oct4 mononuclear factor and SMAD-related TGFβ effector)

differentiation (RUNX1)

and Cell cycle/apoptosis control (p53

p63

and p73 family members). This is due to the diverse roles of YAP and may limit tumor progression and establishment. TEAD also coordinates various signal transduction pathways such as Hippo

WNT

TGFβ and EGFR

and effects on lack of regulation of TEAD cancerous genes

such as KRAS

BRAF

LKB1

NF2 and MYC

which play essential roles in tumor progression

metastasis

cancer metabolism

immunity

and drug resistance. However

RAS signaling is a pivotal factor in the inactivation of Hippo

which controls EGFR-RAS-RAF-MEK-ERK-mediated interaction of Hippo signaling. Thus

the loss of the Hippo pathway may have significant consequences on the targets of RAS-RAF mutations in cancer.