Oncogenic human herpesvirus hijacks proline metabolism for tumorigenesis

• DOI: 10.1073/pnas.1918607117
• Publication Date: 2020-03-26T00:15:34Z
• Authors: Un Yung Choi; Jae Jin Lee; Angela Park; Wei Zhu; Hye-Ra Lee; Youn Jung Choi; Ji-Seung Yoo; Claire Yu; Pinghui Feng; Shou-Jiang Gao; Shaochen Chen; Hyungjin Eoh; Jae U. Jung
• Keywords: 0303 health sciences; Proline; Cell Culture Techniques; Xenograft Model Antitumor Assays; Mice; Viral Proteins; delta-1-Pyrroline-5-Carboxylate Reductase; 03 medical and health sciences; Cell Transformation, Neoplastic; Cell Line, Tumor; Spheroids, Cellular; Herpesvirus 8, Human; Proline Oxidase; Animals; Humans; Metabolomics; Pyrroline Carboxylate Reductases; Sarcoma, Kaposi; Cell Proliferation

Significance While understanding metabolic change of tumor cells is crucial to improve cancer therapy, current 2D cell culture condition may not fully recapitulate in vivo environment tumors. Our metabolomics analysis demonstrates that proline metabolism critical for the KSHV-transformed growth 3D culture, culture. Specifically, KSHV K1 oncoprotein activates PYCR biosynthesis enzyme, increasing intracellular concentration vitro spheroid and tumorigenesis. This study describes an oncogenic strategy enhance synthesis virus-induced transformation, adding pathway as a potential target KS treatment.