Keratin 14-high subpopulation mediates lung cancer metastasis potentially through Gkn1 upregulation.

Abstract

Metastasis is the leading cause of lung cancer-related death. Elucidating the metastasis process can provide new avenues to inhibit this malignant behavior of cancer cells. Here we found that human lung cancers with high Keratin 14 (K14) expression were associated with nodal metastasis and poor survival. Using the KrasG12D/Trp53L/L lung cancer mouse model, we confirmed that K14-high cancer cells harbored increased metastatic potential. Mechanistic investigation revealed that Gastrokine 1 (Gkn1) expression positively correlated with K14 level, cancer metastasis, and poor patient survival. Importantly, ectopic expression of Gkn1 enhanced the metastatic capability of K14-low cells in vitro and in vivo, whereas knockdown of Gkn1 did the opposite, indicating the importance of Gkn1 in mediating the metastasis of K14-high cells. Further study demonstrated that Gkn1 expression conferred K14-high cells resistance to anoikis, which is critical for cancer metastasis. Collectively, our findings demonstrate that K14-high cells contribute to lung cancer metastasis potentially through inhibition of anoikis via upregulation of Gkn1.

• Authors: Shun Yao, Hsin-Yi Huang, Xiangkun Han, Yi Ye, Zhen Qin, Gaoxiang Zhao, Fuming Li, Guohong Hu, Liang Hu, Hongbin Ji
• Journal: Oncogene (Oncogene) Vol. 38 Issue 36 Pg. 6354-6369 (09 2019) ISSN: 1476-5594 [Electronic] England
• PMID: 31320708 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• GKN1 protein, human
• KRAS protein, human
• KRT14 protein, human
• Keratin-14
• Peptide Hormones
• TP53 protein, human
• Tumor Suppressor Protein p53
• Proto-Oncogene Proteins p21(ras)

Topics

• Adenocarcinoma (genetics, mortality, pathology)
• Animals
• Anoikis (genetics)
• Cells, Cultured
• Gene Expression Regulation, Neoplastic
• HEK293 Cells
• Humans
• Keratin-14 (genetics, physiology)
• Lung Neoplasms (genetics, mortality, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Mice, Transgenic
• Neoplasm Metastasis
• Peptide Hormones (genetics, metabolism)
• Proto-Oncogene Proteins p21(ras) (genetics)
• Tumor Suppressor Protein p53 (genetics)
• Up-Regulation (genetics)