Department of Otolaryngology-Head and Neck Surgery, Research Institute for Medical Science, Chungnam National University College of Medicine, Daejeon, Republic of Korea.
Department of Medical Science, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
Sci Rep. 2018 Feb 9;8(1):2718. doi: 10.1038/s41598-018-21216-0.
Laminin subunit beta-3 (LAMB3) encodes one of the three subunits of LM-332, a protein of the extracellular matrix secreted by cultured human keratinocytes. While LAMB3 is involved in the invasive and metastatic abilities of several tumor types, including those found in the colon, pancreas, lung, cervix, stomach, and prostate, its mechanism of action in thyroid cancer has not been investigated previously. Our results show that LAMB3 is up-regulated in papillary thyroid cancer, and that its suppression reduces cell migration/invasion via down-regulation of epithelial‒mesenchymal transition-associated proteins (N-cadherin, vimentin, slug) and inhibition of matrix metalloproteinase 9. LAMB3 suppression also significantly decreases Akt phosphorylation and inhibits the transcription of c-MET, reducing its activation. These results suggest that LAMB3 leads to tumor invasion via Akt activation induced by the HGF/c-MET axis in papillary thyroid cancer cells. Our findings reveal a novel mechanism of action for LAMB3 in papillary thyroid cancer cells.
层粘连蛋白亚基β-3（LAMB3）编码 LM-332 的三个亚基之一，LM-332 是由培养的人角质形成细胞分泌的细胞外基质中的一种蛋白质。虽然 LAMB3 参与了几种肿瘤类型的侵袭和转移能力，包括结肠癌、胰腺癌、肺癌、宫颈癌、胃癌和前列腺癌，但它在甲状腺癌中的作用机制以前尚未被研究过。我们的结果表明，LAMB3 在甲状腺乳头状癌中上调，其抑制作用通过下调上皮-间充质转化相关蛋白（N-钙黏蛋白、波形蛋白、slug）和抑制基质金属蛋白酶 9 来减少细胞迁移/侵袭。LAMB3 的抑制也显著降低 Akt 的磷酸化，并抑制 c-MET 的转录，从而降低其活性。这些结果表明，LAMB3 通过 HGF/c-MET 轴在甲状腺乳头状癌细胞中激活 Akt 导致肿瘤侵袭。我们的发现揭示了 LAMB3 在甲状腺乳头状癌细胞中的一种新的作用机制。
