Lactate-driven type I collagen deposition facilitates cancer stem cell-like phenotype of head and neck squamous cell carcinoma
Yunqing Sun,
Yang Chen,
Hui Zhao,
Jingjing Wang,
Yuantong Liu,
Junqiang Bai,
Chuanyu Hu,
Zhengjun Shang
Affiliations
Yunqing Sun
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
Yang Chen
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Wuhan University, Wuhan, China
Hui Zhao
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Department of Oral and Maxillofacial-Head and Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
Jingjing Wang
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
Yuantong Liu
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
Junqiang Bai
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
Chuanyu Hu
Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, China; Corresponding author
Zhengjun Shang
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Department of Oral and Maxillofacial-Head and Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Corresponding author
Summary: Lactate is known to play a crucial role in the progression of malignancies. However, its mechanism in regulating the malignant phenotype of head and neck squamous cell carcinoma (HNSCC) remains unclear. This study found that lactate increases cancer stem cell (CSC) characteristics of HNSCC by influencing the deposition of type I collagen (Col I). Lactate promotes Col I deposition through two distinct pathways. One is to convert lactate to pyruvate, a substrate for Col I hydroxylation. The other is the activation of HIF1-α and P4HA1, the latter being a rate-limiting enzyme for Col I synthesis. Inhibition of these two pathways effectively counteracts lactate-induced enhanced cell stemness. Further studies revealed that Col I affects CSC properties by regulating cell cycle dynamics. In conclusion, our research proposes that lactate-driven Col I deposition is essential for the acquisition of CSC properties, and lactate-centric Col I deposition may be an effective target for CSCs.
