The significance of SMARCB1 in the pathogenesis of renal cell carcinoma with rhabdoid features

Yi Wen Wang, Hsiang Lin Song, Cheng Yao Chiang, Hong Fang Song, Hong Yi Chang, Chien An Chu, Yih Lin Tuan, Kun Hao Tsai, Yin Chien Ou, Nan Haw Chow, Yuh Shyan Tsai

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Abstract

Background: Renal cell carcinoma with rhabdoid features (RCC-RF) is an aggressive histologic variant in the adults and is usually unresponsive to standard chemotherapy. Methods: Expression of SMARCB1/INI1 was examined in primary RCC-RF (n = 5). Stable INI1 with/without prostaglandin E2 receptor 1 (EP1) knockdown cell lines were created in the ACHN and 786-O RCC cell lines and measured for epidermal growth factor receptor (EGFR)-related signaling pathways. Chemosensitivity to targeted drugs in vitro was tested after knocking down of INI1 in both cell lines. The outcome of co-targeting of INI1 and EP1 in RCC was examined using a tumorigenicity assay. Results: Expression of INI1 was markedly reduced at both transcriptional and translational levels in primary RCC-RF. Immunohistochemical expression of INI1 protein was lost in the nuclei of rhabdoid cells compared with conventional RCC (n = 8). Using two cell lines with different genetic background, we showed that knocking down of INI1 activates the EGFR signaling with up-regulated AKT and ERK pathways and sensitizes cancer cells to Erlotinib treatment in vitro. However, cell-line dependent effects were also demonstrated with reference to impact of INI1 or EP1 on cell growth, migration and response to Gefitinib or Everolimus treatment in vitro. Conclusion: Inactivation of INI1 may play a role in the pathogenesis of RCC-RF. Erlotinib is recommended in the management of patients with INI1-related RCC.

Original languageEnglish
Article number101175
JournalTranslational Oncology
Volume14
Issue number10
DOIs
Publication statusPublished - 2021 Oct

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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