Cytokeratin-14 contributes to collective invasion of salivary adenoid cystic carcinoma

Gao, Xiaolei; Wu, Jian; Cao, Min-xin; Gao, Siyang; Cen, Xiao; Jiang, Yaping; Wang, Shasha; Tang, Ya‐Jie; Chen, Qianming; Liang, Xin‐hua; Tang, Yaling

doi:10.1371/journal.pone.0171341

Cited by 26 publications

(18 citation statements)

References 31 publications

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“…Interestingly, re-expression of basal keratins K5 and K14 reversed these phenotypes [129], indicating that K5 and K14 inhibit cell invasion (Figure 2C). However, in breast cancer, K14 expression in leader cells is required for tumor cells to collectively invade their surrounding microenvironment for metastasis [55], and a similar observation was made using salivary adenoid cystic carcinoma cells in a 3D culture assay (Figure 2A) [130].…”

Section: Impacts Of Intermediate Filament Proteins On Cancer Hallmmentioning

confidence: 76%

Intermediate Filaments as Effectors of Cancer Development and Metastasis: A Focus on Keratins, Vimentin, and Nestin

Sharma

Alsharif

Fallatah

et al. 2019

Cells

121

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Intermediate filament (IF) proteins make up the largest family of cytoskeletal proteins in metazoans, and are traditionally known for their roles in fostering structural integrity in cells and tissues. Remarkably, individual IF genes are tightly regulated in a fashion that reflects the type of tissue, its developmental and differentiation stages, and biological context. In cancer, IF proteins serve as diagnostic markers, as tumor cells partially retain their original signature expression of IF proteins. However, there are also characteristic alterations in IF gene expression and protein regulation. The use of high throughput analytics suggests that tumor-associated alterations in IF gene expression have prognostic value. Parallel research is also showing that IF proteins directly and significantly impact several key cellular properties, including proliferation, death, migration, and invasiveness, with a demonstrated impact on the development, progression, and characteristics of various tumors. In this review, we draw from recent studies focused on three IF proteins most associated with cancer (keratins, vimentin, and nestin) to highlight how several “hallmarks of cancer” described by Hanahan and Weinberg are impacted by IF proteins. The evidence already in hand establishes that IF proteins function beyond their classical roles as markers and serve as effectors of tumorigenesis.

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Section: Impacts Of Intermediate Filament Proteins On Cancer Hallmmentioning

confidence: 76%

Intermediate Filaments as Effectors of Cancer Development and Metastasis: A Focus on Keratins, Vimentin, and Nestin

Sharma

Alsharif

Fallatah

et al. 2019

Cells

121

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“…CK14 is recognized as a specific epithelial marker, particularly of the basal cells [34][35][36]. The increased values in the S group at day 14 support the early appearance of K14 in the differentiation process.…”

Section: Discussionmentioning

confidence: 87%

Palatal Wound Healing with Primary Intention in a Rat Model—Histology and Immunohistomorphometry

et al. 2020

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Background and objectives: Subepithelial connective tissue graft (SCTG) from the palate has been considered as the “gold standard” for the treatment of deep gingival recessions. A single-incision technique was reported to allow primary wound healing. A palatal single incision was performed in a rat model. The present study assessed the histology and histomorphometry of palatal wound healing following surgical closure with primary intention. Materials and Methods: Twenty-six 6-month-old male Wistar rats weighing 427–650 g. An incision was made on the maxillary palate. A full thickness flap was raised palatally, and then repositioned and sutured. Two experimental groups: S—Study group, I—Intact control group. Half of the animals were sacrificed 7 days and the remaining 14 days postoperatively. Outcome parameters included—epithelial gap; inflammatory infiltration; vascular fraction, expression of myofibroblasts and stem cell markers within the oral epithelium and stromal cells and physical properties of stromal collagen fibers. Investigations were performed at two time-points (7 and 14 days) during the wound healing process. Results: The epithelial gap closed completely after 14 days. The inflammatory reaction and vascular fraction were relatively low. Surgical trauma downregulated the expression of cytokeratin (CK) 14 and CK 15, which returned to normal after 14 days. Epithelial differentiation was mediated through upregulation of connective tissue sex- determining-region-Y-box2 (SOX2). Epithelial SOX2, CD34, alpha smooth muscle actin (αSMA) and physical properties of stromal collagen fibers were not influenced by the surgical trauma. Conclusions: Surgical trauma followed by palatal wound healing with primary intention in a rat model heals within 14 days. It induces minimal inflammatory infiltration and vascular proliferation. Epithelization is exerted through promotion of epithelial differentiation from stem cells by connective tissue SOX2.

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“…Leader cells may also secrete immune effector molecules, influencing lymphocyte differentiation and polarizing local immune responses towards a suppressive phenotype [49]. Several studies have now demonstrated the importance of leader cells in the progression of epithelial-tumour types including breast, salivary, bladder, prostate, and lung cancers [36,38,49,50,51].…”

Section: Leader Cells and Progenitor-like Propertiesmentioning

confidence: 99%

Therapeutic Targeting of Collective Invasion in Ovarian Cancer

Moffitt

Karimnia

Stephens

et al. 2019

IJMS

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Ovarian cancer is the seventh most commonly diagnosed cancer amongst women and has the highest mortality rate of all gynaecological malignancies. It is a heterogeneous disease attributed to one of three cell types found within the reproductive milieu: epithelial, stromal, and germ cell. Each histotype differs in etiology, pathogenesis, molecular biology, risk factors, and prognosis. Furthermore, the origin of ovarian cancer remains unclear, with ovarian involvement secondary to the contribution of other gynaecological tissues. Despite these complexities, the disease is often treated as a single entity, resulting in minimal improvement to survival rates since the introduction of platinum-based chemotherapy over 30 years ago. Despite concerted research efforts, ovarian cancer remains one of the most difficult cancers to detect and treat, which is in part due to the unique mode of its dissemination. Ovarian cancers tend to invade locally to neighbouring tissues by direct extension from the primary tumour, and passively to pelvic and distal organs within the peritoneal fluid or ascites as multicellular spheroids. Once at their target tissue, ovarian cancers, like most epithelial cancers including colorectal, melanoma, and breast, tend to invade as a cohesive unit in a process termed collective invasion, driven by specialized cells termed “leader cells”. Emerging evidence implicates leader cells as essential drivers of collective invasion and metastasis, identifying collective invasion and leader cells as a viable target for the management of metastatic disease. However, the development of targeted therapies specifically against this process and this subset of cells is lacking. Here, we review our understanding of metastasis, collective invasion, and the role of leader cells in ovarian cancer. We will discuss emerging research into the development of novel therapies targeting collective invasion and the leader cell population.

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Cytokeratin-14 contributes to collective invasion of salivary adenoid cystic carcinoma

Cited by 26 publications

References 31 publications

Intermediate Filaments as Effectors of Cancer Development and Metastasis: A Focus on Keratins, Vimentin, and Nestin

Intermediate Filaments as Effectors of Cancer Development and Metastasis: A Focus on Keratins, Vimentin, and Nestin

Palatal Wound Healing with Primary Intention in a Rat Model—Histology and Immunohistomorphometry

Therapeutic Targeting of Collective Invasion in Ovarian Cancer

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