[Table/Fig-1]:

Distribution of Sl00 protein, and subunits where known, in normal structures and cells found in and around the head and neck [9,10].

S100 Proteins	Normal Expression	Tumors in which expression is up-regulated	Tumors in which expression is down-regulated	Known interactions / Mechanism of Action / Clinical Implication
S100A1	Heart Less in skeletal muscle	Renal oncocytomas, clear cell and papillary renal cell carcinomas Endometrium subtype of ovarian and endometrial carcinomas	____	A marker for poor prognosis ovarian and endometrial cancers. A specific and sensitive marker in distinguishing nephrogenic adenoma from prostatic adenocarcinoma. Known RAGE ligand.
S100A2	Many organs Increased expression in lungs and kidneys	Non-small cell carcinoma of lung Pancreatic carcinoma Colon carcinoma Gastric carcinoma Thyroid, papillary and anaplastic carcinoma	Larynx carcinoma Oral squamous cell carcinoma Prostate, bladder carcinoma	A poor prognostic marker for NSCLC and pancreatic cancer A predictor of good prognosis and survival in OSCC, ESCC and LSCC. An independent prognostic marker for recurrence in oral cancer and CRC. A predictor of response pancreatectomy and a metastatic marker for pancreatic cancer. Promotes p53 transcriptional activity and reduces expression of COX-2.
S100A3	Hair cuticle	____	Invasive breast tumor	Not known
S100A4 also called Metastatin	Nervous system Expression is low in normal tissues	Breast cancer Colorectal carcinoma Gastric carcinoma Prostate carcinoma Non-small cell carcinoma of lung Ovarian carcinoma Pancreatic carcinoma Melanoma carcinoma	Oral	Promotes tumor migration, invasion and angiogenesis. Regulates matrix metalloproteinases and interacts with p53 and inhibits p53 phosphorylation. Biomarker for metastasis in multiple cancer
S100A5	Restricted regions of the adult brain.	Brain tumors	____	____
S100A6	Epithelial cells Fibroblasts	Colorectal carcinoma Pancreatic carcinoma Gastric carcinoma Hepatocellular carcinoma Lung carcinoma Melanoma	Prostate cancer and Medulloblastomas.	Diagnostic marker or prognostic factor in pancreatic cancer, gastric cancer, prostate cancer, melanoma. Known RAGE ligand.
S100A7 also called psoriasin	Epithelial cells of skin Antibacterial effect	Breast cancer Bladder carcinoma Skin carcinoma Oral carcinoma	Salivary gland carcinoma	A predictor of poor prognosis in HNSCC and estrogen receptor-negative invasive breast cancer. Serum S100A7 may serve as a potentially diagnostic marker for lung cancer and ovarian cancer. Possible interaction with Jab-1.
S100A8	Expressed predominantly by myeloid cells, including granulocytes, monocytes, myeloid derived suppressor cells (MDSC) and other immature cells of myeloid lineage	Gastric carcinoma Colon carcinoma Pancreatic carcinoma Bladder carcinoma Ovarian carcinoma Thyroid carcinoma Breast carcinoma Skin carcinoma	Oral carcinoma Cervix carcinoma	Interaction with RAGE and TLR4; promote tumor proliferation, and migration, accumulation of myeloid derived suppressor cells, activation of protumorigenic genes, and formation of premetastatic niches in distal organs.
S100A9	Expressed predominantly by myeloid cells, including granulocytes, monocytes, myeloid derived suppressor cells (MDSC) and other immature cells of myeloid lineage	Breast cancer Stomach carcinoma Lung carcinoma Cervix carcinoma Prostate carcinoma Oral carcinoma	Esophagus	A poor prognostic marker in IDC and NSCLC; Serum S100A9 may serve as a useful marker to discriminate between prostate cancer and benign prostatic hyperplasia.
S100A10-also known as p11 protein	Predominantly in lungs and kidney Brain	Breast cancer Stomach carcinoma Gallbladder carcinoma Kidney carcinoma	___	A potential molecular target for early gallbladder cancer diagnostics and therapeutic applications.
S100A11	Placenta Heart Lung Kidney	Uterine, smooth muscle carcinoma Lymphoma, anaplastic large cell Pancreatic carcinoma	Bladder carcinoma Esophageal, squamous cell carcinoma	Down-regulation of S100C is associated with bladder cancer progression and poor survival.
S100A13	Thyroid gland Smooth muscle cells	Melanoma	___	An angiogenic and prognostic marker in melanoma.
S100A14	____	Breast cancer Ovary carcinoma Uterus carcinoma	Oral carcinoma Kidney carcinoma Rectum carcinoma Colon carcinoma	Promotes cell motility and invasiveness by regulating the expression and function of MMP2 in a p53-dependent manner.
S100A15 also called as Koebnerisin	Epidermal basal Differentiated keratinocytes, melanocytes Langerhan’s cells	Breast carcinoma	____	Regulates tumor progression Overexpressed in inflammatory skin diseases, such as psoriasis and eczema.
S100A16	Brain (astrocytoma)	Bladder carcinoma Lung carcinoma Thyroid carcinoma Pancreas carcinoma Ovary carcinoma	____	S100A14 and S100A16 might be prognostic biomarkers and potential therapeutic targets for breast cancer
S100B	Brain – highly expressed by astrocytes and schwann cells	Brain – highly expressed by astrocytes and schwann cells	____	Interacts with p53 and down-regulates p53-mediated apoptosis in melanoma. Well known RAGE ligand.
S100P	Placenta GI tract Prostate Leukocyte	Ovarian carcinoma Pancreatic carcinoma Breast cancer Gastric carcinoma Colorectal carcinoma Prostate carcinoma Lung carcinoma	_____	S100P is potentially useful for molecular diagnosis of NSCLCs. Elevated S100P level showed poorer overall survival in CRC and ovarian cancer patients. Activation of RAGE dependent signaling pathways.

NSCLC- Non-Small Cell Lung Cancer, OSCC- Oral Squamous Cell Carcinoma, ESCC- Esophagus Squamous Cell Carcinoma, LSCC- Laryngeal Squamous Cell Carcinoma, CRC- Colorectal Cancer.