TY - CHAP
T1 - Notch signaling and human papillomavirus–associated oral tumorigenesis
AU - Das, Trianth
AU - Zhong, Rong
AU - Spiotto, Michael T.
N1 - Publisher Copyright:
© 2021, Springer Nature Switzerland AG.
PY - 2021
Y1 - 2021
N2 - The NOTCH pathway is critical for the development of many cell types including the squamous epithelium lining of cutaneous and mucosal surfaces. In genetically engineered mouse models, Notch1 acts as one of the first steps to commit basal keratinocytes to terminally differentiate. Similarly, in human head and neck squamous cell cancers (HNSCCs), NOTCH1 is often lost consistent with its essential tumor-suppressive role for initiating keratinocyte differentiation. However, constitutive NOTCH1 activity in the epithelium results in expansion of the spinous keratinocyte layers and impaired terminal differentiation is consistent with the role of NOTCH1 as an oncogene in other cancers, especially in T-cell acute lymphoblastic leukemia. We have previously observed that NOTCH1 plays a dual role as both a tumor suppressor and oncogene, depending on the mutational context of the tumor. Namely, gain or loss or NOTCH1 activity promotes the development of human papillomavirus (HPV)–associated cancers. The additional HPV oncogenes likely disrupt the tumor-suppressive activities of NOTCH and enable the oncogenic pathways activated by NOTCH to promote tumor growth. In this review, we detail the role of NOTCH pathway in head and neck cancers with a focus on HPV-associated cancers.
AB - The NOTCH pathway is critical for the development of many cell types including the squamous epithelium lining of cutaneous and mucosal surfaces. In genetically engineered mouse models, Notch1 acts as one of the first steps to commit basal keratinocytes to terminally differentiate. Similarly, in human head and neck squamous cell cancers (HNSCCs), NOTCH1 is often lost consistent with its essential tumor-suppressive role for initiating keratinocyte differentiation. However, constitutive NOTCH1 activity in the epithelium results in expansion of the spinous keratinocyte layers and impaired terminal differentiation is consistent with the role of NOTCH1 as an oncogene in other cancers, especially in T-cell acute lymphoblastic leukemia. We have previously observed that NOTCH1 plays a dual role as both a tumor suppressor and oncogene, depending on the mutational context of the tumor. Namely, gain or loss or NOTCH1 activity promotes the development of human papillomavirus (HPV)–associated cancers. The additional HPV oncogenes likely disrupt the tumor-suppressive activities of NOTCH and enable the oncogenic pathways activated by NOTCH to promote tumor growth. In this review, we detail the role of NOTCH pathway in head and neck cancers with a focus on HPV-associated cancers.
KW - Head and Neck Cancers
KW - Human papillomavirus 16
KW - NOTCH
UR - http://www.scopus.com/inward/record.url?scp=85092312947&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85092312947&partnerID=8YFLogxK
U2 - 10.1007/978-3-030-55031-8_8
DO - 10.1007/978-3-030-55031-8_8
M3 - Chapter
C2 - 33034029
AN - SCOPUS:85092312947
T3 - Advances in Experimental Medicine and Biology
SP - 105
EP - 122
BT - Advances in Experimental Medicine and Biology
PB - Springer
ER -