The Hippo pathway in chemotherapeutic drug resistance

Abstract

Chemotherapy is one of the major treatments for cancer patients. Although chemotherapeutic drugs can sometimes effectively suppress tumor growth in cancer patients, a significant proportion of patients are either intrinsically resistant or later develop resistance to primary chemotherapy, leading to disease relapse and patient mortality. The best way to conquer the resistance is the better understanding of the molecular network in cancer cells in response to drugs. Therefore, identification of signaling pathways and molecules involved in drug resistance is essential for successful treatment of cancers. The Hippo pathway is an emerging signaling pathway that plays important roles in tumorigenesis, stem cell self‐renewal and differentiation, organ size control as well as many other biological processes. Therefore, exploring novel roles of the Hippo pathway in various biological functions has become one of the cutting‐edge research areas in cancer and other biomedical research. Recently, we and others have provided new evidence that the Hippo pathway is involved in the resistance of different types of cancer cells to various chemotherapeutic drugs. In this review, we will discuss the specific roles of the Hippo pathway in chemotherapy, potential applications for studying this network in response to drugs as well as the future direction in identification of therapeutic targets.

Roles of the Hippo pathway in lung development and tumorigenesis

“…5,7,[16][17][18][19][20][21][22][23][24][25] The core components of this pathway are composed of two serine/threonine (S/T) kinases Mst1 and its homolog Mst2 (mammalian homolog of Drosophila Hippo) and LATS1 and its homolog LATS2, two adaptor/scaffold proteins hMOB1 and WW45 and two WW domaincontaining transcriptional co-activators TAZ and its paralog YAP (Fig. 5,7,[16][17][18][19][20][21][22][23][24][25] The core components of this pathway are composed of two serine/threonine (S/T) kinases Mst1 and its homolog Mst2 (mammalian homolog of Drosophila Hippo) and LATS1 and its homolog LATS2, two adaptor/scaffold proteins hMOB1 and WW45 and two WW domaincontaining transcriptional co-activators TAZ and its paralog YAP (Fig.…”

Long-Term Exposure to Imatinib Mesylate Downregulates Hippo Pathway and Activates YAP in a Model of Chronic Myelogenous Leukemia

“…It is crucial for tissue homeostasis, cell proliferation, development, and stem cell renewal [61]. It has recently been recognized to have a role in cancer and chemoresistance [55,62]. Although the core Hippo pathway has been characterized, the regulatory mechanisms that affect this signaling cascade are poorly understood.…”

Hippo Component TAZ Functions as a Co-repressor and Negatively Regulates ΔNp63 Transcription through TEA Domain (TEAD) Transcription Factor

“…It is proposed as a major regulator of cell proliferation, cell migration and invasion, epithelial-mesenchymal transition (EMT), human embryonic stem cell renewal, and drug resistance (21)(22)(23)(24)(25)(26)(27). Within the N terminus of TAZ lies a TEAD binding domain (TBD) responsible for the interaction with the TEAD family of transcription factors.…”