CD271 is a negative prognostic factor and essential for cell proliferation in lung squamous cell carcinoma.

Abstract

Squamous cell carcinoma is a major type of cancer in the lung. While several therapeutic target molecules for lung adenocarcinoma have been identified, little is known about lung squamous cell carcinoma (LSCC). We recently reported that CD271 (p75 neurotrophin receptor) serves as a marker for tumor initiation and is a key regulator of cell proliferation in hypopharyngeal squamous cell carcinoma. In this study, we found that CD271 was also expressed in squamous cell carcinoma, but not in adenocarcinoma, of several tissues, including the lung, and the expression of CD271 was associated with a poor prognosis in LSCC. To examine CD271's role in LSCC, we established xenograft cell lines from LSCC patients. Within the sorted live LSCC cell population, the CD271high cells were primarily cycling through the G2/M phase, while the CD271low cells were mostly in the G0 phase. CD271 knockdown in the LSCC cells completely suppressed their proliferation and tumor-formation capability, and increased their cell-cycle arrest in the G0 phase. In the CD271-knockdown cells, ERK-phosphorylation was decreased, while no change was observed in the IκBα-phosphorylation, p65-phosphorylation, or Akt-phosphorylation. Treatment with the MEK inhibitor U0126 decreased the LSCC cells' proliferation capability. Microarray analysis revealed that CD271 knockdown attenuated the RAS-related pathways. The knockdown of TrkB, which forms a heterodimer with CD271 and accelerates its downstream signaling, partially inhibited the LSCC cell proliferation. These results indicated that LSCC exclusively depends on CD271 for cell proliferation, in part through ERK-signaling activation, and CD271 is a promising target for LSCC therapy.

• Authors: Mai Mochizuki, Mao Nakamura, Rie Sibuya, Toshimasa Okazaki, Jiro Abe, Takayuki Nakagawa, Satomi Takahashi, Tomoko Yamazaki, Takayuki Imai, Atsushi Takano, Hiroyuki Ito, Tomoyuki Yokose, Yohei Miyagi, Yataro Daigo, Ikuro Sato, Kennichi Satoh, Kazuo Sugamura, Kazunori Yamaguchi, Keiichi Tamai
• Journal: Laboratory investigation; a journal of technical methods and pathology (Lab Invest) Vol. 99 Issue 9 Pg. 1349-1362 (09 2019) ISSN: 1530-0307 [Electronic] United States
• PMID: 31019292 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• NGFR protein, human
• Nerve Tissue Proteins
• Receptors, Nerve Growth Factor

Topics

• Aged
• Aged, 80 and over
• Animals
• Biomarkers, Tumor
• Carcinoma, Squamous Cell (diagnosis, metabolism, mortality)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Disease-Free Survival
• Female
• Humans
• Lung Neoplasms (diagnosis, metabolism, mortality)
• Male
• Mice, Inbred NOD
• Mice, SCID
• Middle Aged
• Nerve Tissue Proteins (genetics, metabolism)
• Prognosis
• Receptors, Nerve Growth Factor (genetics, metabolism)