Receptor, Signal, Nucleus, Action: Signals That Pass through Akt on the Road to Head and Neck Cancer Cell Migration

TY - JOUR

T1 - Receptor, Signal, Nucleus, Action

T2 - Signals That Pass through Akt on the Road to Head and Neck Cancer Cell Migration

AU - Alzawi, Albashir

AU - Iftikhar, Anem

AU - Shalgm, Basher

AU - Jones, Sarah

AU - Ellis, Ian

AU - Islam, Mohammad

N1 - Funding Information: AI is funded by the University of Dundee Global Challenges Research Funding Scholarship. AA (grant number 13272) and BS (grant number 12931) are funded by the Cultural Attaché, Libyan embassy, London. AA is also funded by Ernst Maas Educational Trust

PY - 2022/5/25

Y1 - 2022/5/25

N2 - This review aims to provide evidence for the role of the tumour microenvironment in cancer progression, including invasion and metastasis. The tumour microenvironment is complex and consists of tumour cells and stromal-derived cells, in addition to a modified extracellular matrix. The cellular components synthesise growth factors such as EGF, TGFα and β, VEGF, and NGF, which have been shown to initiate paracrine signalling in head and neck cancer cells by binding to cell surface receptors. One example is the phosphorylation, and hence activation, of the signalling protein Akt, which can ultimately induce oral cancer cell migration in vitro. Blocking of Akt activation by an inhibitor, MK2206, leads to a significant decrease, in vitro, of cancer-derived cell migration, visualised in both wound healing and scatter assays. Signalling pathways have therefore been popular targets for the design of chemotherapeutic agents, but drug resistance has been observed and is related to direct tumour-tumour cell communication, the tumour-extracellular matrix interface, and tumour-stromal cell interactions. Translation of this knowledge to patient care is reliant upon a comprehensive understanding of the complex relationships present in the tumour microenvironment and could ultimately lead to the design of efficacious treatment regimens such as targeted therapy or novel therapeutic combinations.

AB - This review aims to provide evidence for the role of the tumour microenvironment in cancer progression, including invasion and metastasis. The tumour microenvironment is complex and consists of tumour cells and stromal-derived cells, in addition to a modified extracellular matrix. The cellular components synthesise growth factors such as EGF, TGFα and β, VEGF, and NGF, which have been shown to initiate paracrine signalling in head and neck cancer cells by binding to cell surface receptors. One example is the phosphorylation, and hence activation, of the signalling protein Akt, which can ultimately induce oral cancer cell migration in vitro. Blocking of Akt activation by an inhibitor, MK2206, leads to a significant decrease, in vitro, of cancer-derived cell migration, visualised in both wound healing and scatter assays. Signalling pathways have therefore been popular targets for the design of chemotherapeutic agents, but drug resistance has been observed and is related to direct tumour-tumour cell communication, the tumour-extracellular matrix interface, and tumour-stromal cell interactions. Translation of this knowledge to patient care is reliant upon a comprehensive understanding of the complex relationships present in the tumour microenvironment and could ultimately lead to the design of efficacious treatment regimens such as targeted therapy or novel therapeutic combinations.

KW - tumour microenvironment

KW - extracellular matrix

KW - growth factors

KW - cell migration

KW - Akt

KW - head and neck cancer

UR - https://www.scopus.com/pages/publications/85130785475

U2 - 10.3390/cancers14112606

DO - 10.3390/cancers14112606

M3 - Review article

C2 - 35681586

SN - 2072-6694

VL - 14

JO - Cancers

JF - Cancers

IS - 11

M1 - 2606

ER -