Transforming growth factor‑β signaling in head and neck squamous cell carcinoma: Insights into cellular responses (Review)

Abstract

Head and neck squamous cell carcinoma (HNSCC) arises in the oral cavity, salivary glands, larynx, pharynx, nasal cavity and paranasal sinuses, and is characterized by high morbidity and metastasis rates. Transforming growth factor-β (TGF-β) is a homodimeric protein known to be a multifunctional regulator in target cells and to serve a pivotal role in numerous types of cancer, including HNSCC. The role of TGF-β signaling in carcinogenesis can change from tumor-suppressing to tumor-promoting. In addition, TGF-β induces epithelial-mesenchymal transition and restrains immune surveillance on malignant cells. In the present review, the effects of TGF-β signaling at a cellular level were discussed, which includes the regulation of tumor cells, immune cells and other stromal cells, as well as the possible mechanisms underlying the conversion from a tumor suppressor to a tumor promoter in HNSCC. Further research is required to improve the understanding on how this network is involved in carcinogenesis, progression and metastases in HNSCC.

Index of Cancer-Associated Fibroblasts Is Superior to the Epithelial–Mesenchymal Transition Score in Prognosis Prediction

“…We were aware that several obvious caveats are inherent to the NOG xenograft study, including the fact that the lack of complete immune systems and human orthologous genes might not be entirely functional in mice. Through the literature search, we chose the TGFβ signaling pathway for further in-depth study since it is evolutionarily conserved in humans and mice [ 16 ], and has been repeatedly documented in head and cancer pathogenesis [ 18 , 32 , 33 , 34 , 35 ]. First, we consulted the single-cell RNA-seq dataset GSE103322, comprising ~6000 malignant and non-malignant cells from 18 OSCC tissues, for the cell types that express genes of our interest.…”

Krüppel‐like factor 4 regulates stemness and mesenchymal properties of colorectal cancer stem cells through the TGF‐β1/Smad/snail pathway

“…8,9 For example, in CRC, TGF-β1 highly expression promoted cancer progression by Smad signalling. 8,9 For example, in CRC, TGF-β1 highly expression promoted cancer progression by Smad signalling.…”

TGF-Beta-Activated Cancer-Associated Fibroblasts Limit Cetuximab Efficacy in Preclinical Models of Head and Neck Cancer

“…Specifically, the TGF-beta signaling pathway was upregulated after cetuximab treatment in the stroma of Cetuximab Prog -PDX, whereas in the two Cetuximab Sen -PDXs, downregulation of the same pathway was observed ( Figure 2C). TGF-beta plays a crucial role in TME, mediating both immunosuppression and inducing epithelial-mesenchymal transition (EMT) [43,44], and is known to be secreted by CAFs (Reviewed in [45,46]). CAFs are an important component in the TME that play a pivotal role in tumor cell proliferation, invasion, and metastasis in multiple cancer types [47][48][49][50] including HNC [51,52].…”

“…Besides the involvement of CAFs in promoting tumor cell proliferation, and thus limiting the efficacy of cetuximab, CAFs were shown to reduce NK mediating ADCC by downregulation of the NKG2D receptor [59]. A similar reduction in NKG2D expression and a reduction in ADCC can be induced by TGF-beta [31,[60][61][62], which can also be secreted by CAFs (reviewed in [44,63]). Our results suggest a similar link between TGF-beta and NK cell activity, as in addition to the upregulation of the TGF-beta signaling pathway in Cetuximab Prog -PDX, a downregulation of NK cell-mediated cytotoxicity pathway was found in the RNA-seq.…”