2. Academic Validation
  3. FAM83D promotes epithelial-mesenchymal transition, invasion and cisplatin resistance through regulating the AKT/mTOR pathway in non-small-cell lung cancer

FAM83D promotes epithelial-mesenchymal transition, invasion and cisplatin resistance through regulating the AKT/mTOR pathway in non-small-cell lung cancer

  • Cell Oncol (Dordr). 2020 Jun;43(3):395-407. doi: 10.1007/s13402-020-00494-9.
Chunli Yin 1 2,  Xiaoyan Lin 3,  Yige Wang 1,  Xianqiang Liu 4,  Yi Xiao 1,  Jingchao Liu 5,  Antoine M Snijders 6,  Guangwei Wei 1,  Jian-Hua Mao 7,  Pengju Zhang 8
Affiliations

Affiliations

  • 1 Key Laboratory Experimental, Teratology of the Ministry of Education, Department of Biochemistry and Molecular Biology, Shandong University School of Basic Medical Sciences, 44 Wenhua Xi Road, Jinan, 250012, Shandong, China.
  • 2 Shandong Medical College, Linyi, China.
  • 3 Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, Shandong, China.
  • 4 Department of Breast and thyroid Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, Shandong, China.
  • 5 Department of Urology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China.
  • 6 Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
  • 7 Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA. [email protected].
  • 8 Key Laboratory Experimental, Teratology of the Ministry of Education, Department of Biochemistry and Molecular Biology, Shandong University School of Basic Medical Sciences, 44 Wenhua Xi Road, Jinan, 250012, Shandong, China. [email protected].
PMID: 32006253 DOI: 10.1007/s13402-020-00494-9
Abstract

Purpose: FAM83D has been proposed to act as an oncoprotein in several types of human Cancer. Its role and mode of action in human non-small cell lung Cancer (NSCLC) metastasis and its impact on chemotherapy are as yet, however, poorly understood.

Methods: FAM83D expression was measured in NSCLC cells and normal lung epithelial cells, as well as in primary NSCLC tissues and corresponding adjacent non-cancerous tissues, using qRT-PCR, Western blotting and immunohistochemistry. FAM83D was stably overexpressed in BEAS2B cells or silenced in A549 and H1299 cells using retroviral or lentiviral vectors. The growth capacity of NSCLC cells was evaluated using MTT and colony formation assays. Epithelial-mesenchymal transition (EMT) was assessed using Western blotting and immunofluorescence. NSCLC cell invasive capacities were assessed using scratch wound healing and Boyden chamber assays. NSCLC cell viability in response to cisplatin treatment was assessed using MTT assays in vitro and a xenograft model in vivo.

Results: We found that FAM83D expression levels were significantly elevated in NSCLC cells and tissues, and positively correlated with tumor progression and a poor prognosis. Exogenous FAM83D overexpression promoted, while FAM83D silencing inhibited NSCLC cell proliferation, EMT and invasion. FAM83D silencing also reduced cisplatin resistance. Concordantly, we found that NSCLC patients with a low FAM83D expression benefited most from chemotherapy. Mechanistically, we found that FAM83D activated the protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. Pharmacological treatment with either Akt or mTOR inhibitors reverted FAM83D-induced tumorigenic phenotypes.

Conclusions: Our results suggest a role of FAM83D in NSCLC development. In addition, our results indicate that NSCLC patients exhibiting FAM83D overexpression are likely to benefit from Akt and/or mTOR Inhibitor treatment.

Keywords

AKT/mTOR pathway; Cell migration and invasion; Chemo-resistance; Epithelial-mesenchymal transition; FAM83D; Non-small cell lung cancer.

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