2. Academic Validation
  3. FAXC depletion contributes to tumor progression via the c-MET pathway in renal cell carcinoma

FAXC depletion contributes to tumor progression via the c-MET pathway in renal cell carcinoma

  • Biochem Biophys Res Commun. 2025 Sep 8:778:152388. doi: 10.1016/j.bbrc.2025.152388.
Masato Konno 1,  Haruna Fujimori 2,  Shin-Ichiro Kanno 3,  Rie Shibuya-Takahashi 4,  Mai Mochizuki 4,  Kazunori Yamaguchi 5,  Jun Yasuda 5,  Shigekazu Murakami 4,  Kennichi Satoh 6,  Hisanobu Adachi 7,  Akihiro Ito 8,  Keiichi Tamai 9,  Naoki Asano 10
Affiliations

Affiliations

  • 1 Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, 47-1 Nodayama, Medeshima-Shiote, Natori, Miyagi, 981-1293, Japan; Division of Urology, Miyagi Cancer Center, 47-1 Nodayama, Medeshima-Shiote, Natori, Miyagi, 981-1293, Japan; Department of Urology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan.
  • 2 Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, 47-1 Nodayama, Medeshima-Shiote, Natori, Miyagi, 981-1293, Japan. Electronic address: haruna-huzimori@miyagi-pho.jp.
  • 3 IDAC Fellow Research Group for DNA Repair and Dynamic Proteome Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai, Japan.
  • 4 Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, 47-1 Nodayama, Medeshima-Shiote, Natori, Miyagi, 981-1293, Japan.
  • 5 Division of Molecular and Cellular Oncology, Miyagi Cancer Center Research Institute, 47-1 Nodayama, Medeshima-Shiote, Natori, Miyagi, 981-1293, Japan.
  • 6 Division of Gastroenterology, Tohoku Medical and Pharmaceutical University, 1-15-1, Fukumuro, Miyagino-ku, Sendai, Miyagi, 983-8536, Japan.
  • 7 Division of Urology, Miyagi Cancer Center, 47-1 Nodayama, Medeshima-Shiote, Natori, Miyagi, 981-1293, Japan.
  • 8 Department of Urology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan.
  • 9 Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, 47-1 Nodayama, Medeshima-Shiote, Natori, Miyagi, 981-1293, Japan; Department of Gastroenterology, JR Sendai Hospital, 1-1-5 Itsutsubashi, Aoba-ku, Sendai, Miyagi, 980-0022, Japan.
  • 10 Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, 47-1 Nodayama, Medeshima-Shiote, Natori, Miyagi, 981-1293, Japan; Division of Carcinogenesis and Senescence Biology, Tohoku University Graduate School of Medicine, 47-1 Nodayama, Medeshima-Shiote, Natori, Miyagi, 981-1293, Japan.
PMID: 40706244 DOI: 10.1016/j.bbrc.2025.152388
Abstract

Renal cell carcinoma (RCC), the most common types of kidney Cancer, still requires novel therapeutic targets to improve patients' outcome. In this study, we focus on Failed Axon Connections Homolog (FAXC) gene, a newly identified and potentially important Cancer target, and investigated its detailed role in RCC. In RCC cells, FAXC knockdown resulted in increased cell proliferation, and elevated c-MET expression and phosphorylation. Blockade of c-MET phosphorylation inhibited cell proliferation promoted by FAXC knockdown. In contrast, FAXC overexpression reduced cell proliferation and downregulated c-MET expression in RCC cells. We also found that FAXC is localized to the mitochondria in RCC cells. Additionally, an investigation of RCC patient specimens revealed that FAXC expression was negatively correlated with c-MET phosphorylation and was downregulated in tumor region compared with adjacent normal tissues. Taken together, our findings indicate that FAXC depletion promotes cell proliferation through the activation of c-MET in RCC cells.

Keywords

FAXC; Renal cell carcinoma; c-MET.

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