KRT17 Accelerates Cell Proliferative and Invasive Potential of Laryngeal Squamous Cell Carcinoma (LSCC) through Regulating AKT/mTOR and Wnt/β-Catenin Pathways

Abstract

Background. Laryngeal squamous cell carcinoma (LSCC) is a prevalent malignant tumor of the head and neck with a dismal prognosis. Keratin17 (KRT17) has been proven to serve as an oncogene in various cancers, but it has never been explored in LSCC. We proposed to assess the impact and possible mechanisms of KRT17 in the development of LSCC. Methods. Quantitative reverse transcription-PCR (qRT-PCR) was utilized to examine the mRNA levels. The Kaplan–Meier method was used to calculate the relationship between KRT17 expression and survival curves in LSCC patients. Cell counting kit-8 (CCK-8), colony formation, and flow cytometry assays were utilized to estimate LSCC cell proliferation. The migration and invasion abilities of LSCC cells were ascertained by wound-healing and transwell assays. Immunohistochemical and western blot assays were utilized to appraise protein levels. The xenograft tumor model was used to determine the effect of KRT17 on tumor growth. Results. In the present study, KRT17 was extremely high in LSCC tissues and cells and correlated with a poor prognosis. Inhibition of KRT17 weakens cell proliferative, migratory, and invasive abilities in LSCC and contributes to cell cycle arrest. Besides, we approved that knockdown of KRT17 extraordinarily restrained the xenograft tumor growth in vivo. We preliminarily investigated the role of KRT17 on the AKT/mTOR and Wnt/β-catenin signaling axes and found that these signaling pathways were largely blocked by KRT17 deletion. Conclusion. Collectively, we uncovered that exhaustion of KRT17 suppresses LSCC progression through coordinating AKT/mTOR and Wnt/β-catenin signaling axes, illustrating KRT17 as a promising biomarker for making strides in LSCC treatment.

Emerging Prognostic and Predictive Significance of Stress Keratin 17 in HPV-Associated and Non HPV-Associated Human Cancers: A Scoping Review

“…In HPV-associated cancers, seven (12.5%) studies investigated the prognostic role of K17 in HNSCC [24,[38][39][40][41][42]52] and three (5.4%) studies in cervical SCC [22,34,53]. One study (1.8%) in HNSCC investigated both the prognostic and predictive role [15].…”

“…The details of biomarker assessment methodologies are presented in Supplemental Table S2. Studies investigating K17 at the transcriptome level (n = 24) have found K17 to hold negative prognostic value in most cancer entities (endometrial [30,71], esophageal [57], gastric [72], HNSCC [38,42,52], lung cancer [73,74], melanoma [75,76], pancreatic adenocarcinoma [50,51], and renal cell carcinoma [77]). In TNBC, a negative correlation between K17 RNA expression and outcome was found only in a subgroup of patients with invasive ductal carcinoma with large tumors and advanced stage [29].…”

“…Thirteen studies (56.5%) were based on data derived from The Cancer Genome Atlas (TCGA) [30,31,49,50,57,71,71,73,75,76,80]. Five studies (21.7%) generated their own transcriptome data [38,42,51,52,79]. Thirteen studies reported an effect size in their findings [30,31,42,50,57,65,71,72,75,[78][79][80][81].…”

MicroRNA-485-5p targets keratin17 to regulate pancreatic cancer cell proliferation and invasion via the FAK / SRC / ERK pathway

“…The mechanism of KRT17 regulating tumor progression is tissue specific [18,19]. For instance, KRT17 enhances the proliferation of oral cancer by up-regulating Akt/mTOR signal pathway and suppresses the content of cleaved-caspase-3 to strengthen its function [20]. Tissue-specific cytokine polarization can be induced by low expression of KRT17 in cervical cancer and it is necessary to recruit effector immune cells to vulnerable cervical epithelial cells to prevent the growth of cancer [21].…”

MicroRNA-485-5p targets keratin17 to regulate pancreatic cancer cell proliferation and invasion via the FAK / SRC / ERK pathway

“…The mechanism of KRT17 regulating tumor progression is tissue speci c [18,19]. For instance, KRT17 enhances the proliferation of oral cancer by up-regulating Akt/mTOR signal pathway and suppresses the content of cleaved-caspase-3 to strengthen its function [20]. Tissue-speci c cytokine polarization can be induced by low expression of KRT17 in cervical cancer and it is necessary to recruit effector immune cells to vulnerable cervical epithelial cells to prevent the growth of cancer [21].…”